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Anti-arthrotic and immunmodulatory activity

Chapter

Abstract

Multifactorial causes can lead to osteoarthritis (OA), and its pathogenesis is not clearly understood as yet. The main characteristics of OA are the slowly progressing deterioration of the articular cartilage, accompanied by intermitted painful inflammatory episodes, and a continuous subchondral bone remodeling, often resulting in osteophyte formation in nonweight-bearing joint areas. Because of the lack of innervation and vascularization of cartilage, the destruction of this specific tissue remains unnoticed until other joint compartments are involved such as synovial membranes, answering with reactive synovitis to cartilage debris, or mechanoreception changes in the underlying bone, or until the diminution of articular cartilage results in a radiographically detectable joint space narrowing.

Keywords

Articular Cartilage Graft Versus Host Disease Experimental Allergic Encephalomyelitis Adjuvant Arthritis Tiaprofenic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Akatsuka M, Yamamoto Y, Tobetto K, Yasui T, Ando T (1993) In vitro effects of hyalurononan on prostaglandin E2 induction by interleukin-I in rabbit articular chondrocytes. Agents Actions 38: 122–125PubMedCrossRefGoogle Scholar
  2. Bulstra SK, Kuijer R, Buurman WA, Terwindt-Rouwenhorst E, Guelen PJM, van der Linden AJ (1992) The effect of piroxicam on the metabolism of isolated human chondrocytes. Clin Orthop 277: 289–296PubMedGoogle Scholar
  3. Collier S, Ghosh P (1991) Comparison of the effects of non-steroidal anti-inflammatory drugs ( NSAIDs) on proteoglycan synthesis by articular cartilage explant and chondrocyte monolayer cultures. Biochem Pharmacol 41: 1375–1384Google Scholar
  4. Green GD, Chipman SD, Birkhead JR, Troubetskoy OV, Goldring MB (1995) Interleukin-1 modulation of matrix metalloprotease and proteoglycan expression in human chondrocytes immortalized by simian virus 40. Trans Orthop Res Soc 20: 334Google Scholar
  5. Ismaiel S, Hollander AP, Atkins RM, Elson CJ (1991) Differential responses of human and rat cartilage to degrading stimuli in-vitro. J Pharm Pharmacol 43: 207–209PubMedCrossRefGoogle Scholar
  6. Korver GHV, van de Stadt RJ, van Kampen GPJ, Kiljan E, van der Korst JK (1989) Bovine sesamoid bones: a culture system for anatomically intact articular cartilage. In Vitro Cell Dev Biol 25: 1099–1106Google Scholar
  7. Mohamed-Ali H (1992) Influence of synovial cells on cartilage in vitro: induction of breakdown and inhibition of synthesis. Virchows Archiv B Cell Pathol 62: 227–236CrossRefGoogle Scholar
  8. Seed MP, Ismaiel S, Cheung CY, Thomson TA, Gardner CR, Atkins RM, Elson CJ (1993) Inhibition of interleukin lß induced rat and human cartilage degradation in vitro by the metalloproteinase inhibitor U27391. Ann Rheum Dis 52: 37–43PubMedCrossRefGoogle Scholar
  9. Seong SC, Matsumura T, Lee FY, Whelan MC, Li XQ, Trippel SB (1994) Insulin-like growth factor I regulation of swarm rat chondrosarcoma chondrocytes in culture. Exp Cell Res 211: 238–244PubMedCrossRefGoogle Scholar
  10. Shimazu A, Jikko A, Iwamoto M et. al (1993) Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines. Arthr Rheum 36: 247–253CrossRefGoogle Scholar
  11. Srinivas GR, Chichester CO, Barrach HJ, Matoney AL (1994) Effects of certain antiarthritic agents on the synthesis of type Il collagen and glycosaminoglycans in rat chondrosarcoma cultures. Agents Actions 41: 193–199PubMedCrossRefGoogle Scholar
  12. Venn G, Lauder RM, Hardingham TE, Muir H (1990) Effects of catabolic and anabolic cytokines on proteoglycan biosynthesis in young, old and osteoarthritic canine cartilage. Biochem Soc Trans 18: 973–974PubMedGoogle Scholar
  13. Verschure PJ, van der Kraan PM, Vitters EL, van den Berg WB (1994) Stimulation of proteoglycan synthesis by triamcinolone acetonide and insulin-like growth factor 1 in normal and arthritic murine articular cartilage. J Rheumatol 21: 920–926PubMedGoogle Scholar
  14. Vignon E, Mathieu P, Louisot P, Richard M (1991) In vitro effect of nonsteroidal antiinflammatory drugs on proteoglycanase and collagenase activity in human osteoarthritic cartilage. Arthr Rheum 34: 1332–1335CrossRefGoogle Scholar
  15. Yu LP, Jr, Smith GN, Jr, Hasty KA, Brandt KD (1991) Doxycycline inhibits type XI collagenolytic activity of extracts from human osteoarthritic cartilage and of gelatinase. J Rheumatol 18: 1450–1452PubMedGoogle Scholar
  16. Zafarullah M, Martel-Pelletier J, Cloutier JM, Gedamu L, Pelletier JP (1992) Expression of c-fos, c-jun, jun-B, metallothionein and metalloproteinase genes in human chondrocyte. FEBS 306: 169–172CrossRefGoogle Scholar
  17. Archer CW, McDowell J, Bayliss MT, Stephens MD, Bentley G (1990) Phenotypic modulation in sub-populations of human articular chondrocytes in vitro. J Cell Sci 97: 361–371PubMedGoogle Scholar
  18. Aydelotte MB, Greenhill RR, Kuettner KE (1988) Differences between sub-populations of cultured bovine articular chondrocytes. II. Proteoglycan metabolism. Conn Tiss Res 18: 223–234Google Scholar
  19. Aydelotte MB, Kuettner KE (1988) Differences between sub-populations of cultured bovine articular chondrocytes. I. Morphology and cartilage matrix production. Conn Tiss Res 18: 205–222Google Scholar
  20. Aydelotte MB, Raiss RX, Caterson B, Kuettner KE (1992) Influence of interleukin-1 on the morphology and proteoglycan metabolism of cultured bovine articular chondrocytes. Conn Tiss Res 28: 143–159CrossRefGoogle Scholar
  21. Bassleer C, Henrotin Y, Franchimont P (1990) In vitro assays of chondrocyte functions: the influence of drugs and hormones. Scand J Rheumatology (Suppl 81 ): 13–20CrossRefGoogle Scholar
  22. Bassleer CT, Henrotin YE, Reginster JYL, Franchimont PP (1992) Effects of tiaprofenic acid and acetylsalicylic acid on human articular chondrocytes in 3-dimensional culture. J Rheumatol 19: 1433–1438PubMedGoogle Scholar
  23. Benya PD, Schaffer JD (1982) Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30: 215–224PubMedCrossRefGoogle Scholar
  24. Bonaventure J, Kadhom N, Cohen-Solal L, Ng KH, Bourguignon J, Lasselin C, Freisinger P (1994) Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads. Exp Cell Res 212: 97–104PubMedCrossRefGoogle Scholar
  25. Guo J, Jourdian GW, MacCallum DK (1989) Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Conn Tiss Res 19: 277–297CrossRefGoogle Scholar
  26. Häuselmann HJ, Fernandes RJ, Mok SS, Schmid TM, Block JA, Aydelotte MB, Kuettner KE, Thonar EJMA (1994) Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads. J Cell Sci 107: 17–27PubMedGoogle Scholar
  27. Henrotin Y, Bassleer C, Franchimont P(1992) In vitro effects of etodolac and acetylsalicylic acid on human chondrocyte metabolism. Agents Actions 36:317–323Google Scholar
  28. Jortikka M, Lammi MJ, Parkkinen JJ, Lahtinen R, Tammi MI (1993) A high sensitivity dot-blot assay for proteoglycans by cuprolinic blue precipitation. Conn Tiss Res 29: 263–272CrossRefGoogle Scholar
  29. Kolibas LM, Goldberg RL (1989) Effect of cytokines and anti-arthritic drugs on glycosaminoglycan synthesis by bovine articular chondrocytes. Agents Actions 27: 245–249PubMedCrossRefGoogle Scholar
  30. Lane NE, Williams III RJ, Schurman DJ, Smith RL (1992) Inhibition of interleukin 1 induced chondrocyte protease activity by a corticosteroid and a nonsteroidal antiinflammatory drug. J Rheumatol 19: 135–139PubMedGoogle Scholar
  31. Malemud CJ, Stevenson S, Mehraban F, Papay RS, Purchio AF, Goldberg VM (1994) The proteoglycan synthesis repertoire of rabbit chondrocytes maintained in type II collagen gels. Osteoarthritis and Cartilage 2: 29–42PubMedCrossRefGoogle Scholar
  32. McCollum R, Martel-Pelletier J, DiBattista J, Pelletier JP (1991) Regulation of interleukin 1 receptors in human articular chondrocytes. J Rheumatol (Suppl 27 ) 18: 85–88Google Scholar
  33. Seid JM, Rahman S, Graveley R, Bunning RAD, Nordmann R, Wishart W, Russel RG (1993) the effect of interleukin-1 on cytokine gene expression in cultured human articular chondrocytes analyzed by messenger RNA phenotyping. Arthritis and Rheumatism 36: 35–43Google Scholar
  34. van der Kraan P, Vitters E, van den Berg W (1992) Differential effect of transforming growth factor ß on freshly isolated and cultured articular chondrocytes. J Rheumatol 19: 140–145PubMedGoogle Scholar
  35. Verbruggen G, Veys EM, Wieme N, Malfait AM, Gijselbrecht L, Nimmegeers J, Almquist KF, Broddelez C (1990) The synthesis and immobilisation of cartilage-specific proteoglycan by human chondrocytes in different concentrations of agarose. Clin Exp Rheumatol 8: 371–378PubMedGoogle Scholar
  36. Aydelotte MB, Schleyerbach R, Zeck BJ, Kuettner KE (1986) Articular chondrocytes cultured in agarose gel for study of chondrocytic chondrolysis. In: Kuettner (ed) Articular Cartilage Biochemistry. Raven Press, New York, pp 235–256Google Scholar
  37. Oestensen M, Veiby OP, Raiss R, Hagen A, Pahle J (1991) Responses of normal and rheumatic human articular chondrocytes cultured under various experimental conditions in agarose. Scand J Rheumatol 20: 172–182.CrossRefGoogle Scholar
  38. Raiss RX, Karbowski A, Aigner T, Schleyerbach R (1995) Chondrocytes and antirheumatic drugs. J Rheumatol (Suppl 43 ) 22: 152–154Google Scholar
  39. Raiss RX, Oestensen M, Aydelotte MB (1992) Drug evaluation on isolated articular chondrocytes. In: Kuettner K et al, eds. Articular Cartilage and Osteoarthritis, Raven Press Ltd, New York pp. 569–582Google Scholar
  40. Verbruggen G, Veys EM, Malfait AM, Schatteman L, Wieme N, Heynen G, Vanhoutte V, Broddelez C (1989) Proteoglycan metabolism in isolated chondrocytes from human cartilage and in short-term tissue-cultured human articular cartilage. Clin Exp Rheumatol 7: 13–17PubMedGoogle Scholar
  41. Chayen J, Bitensky L, Mehdizadeh S, Dunham J, Older J (1994) Testing drugs on human osteoarthritic articular cartilage. Cell Biochem Funct 12: 63–68PubMedCrossRefGoogle Scholar
  42. Lafeber FPG, van Roy H, Wilbrink B, Huber-Bruning O, Bijlsma JWJ (1992) Human osteoarthritic cartilage is synthetically more active but in culture less vital than normal cartilage. J Rheumatol 19: 123–129PubMedGoogle Scholar
  43. Lafeber FPJG, van der Kraan PM, van Roy JLAM, Huber-Bruning O, Bijlsma JWJ (1993) Articular cartilage explant culture; an appropriate in vitro system to compare osteoarthritic and normal human cartilage. Conn Tiss Res 29: 287–299CrossRefGoogle Scholar
  44. McQuillan DJ, Handley CJ, Robinson HC (1986) Control of proteoglycan biosynthesis. Biochem J 237: 741–747PubMedGoogle Scholar
  45. Nixon JS, Bottomley KMK, Broadhust MJ et. al (1991) Potent collagenase inhibitors prevent interleukin-1-induced cartilage degradation in vitro. Int J Tiss Reac 13: 237–243Google Scholar
  46. Pelletier JP, Cloutier JM, Martel-Pelletier J (1989) In vitro effects of tiaprofenic acid, sodium salicylate and hydrocortisone on the proteoglycan metabolism of human osteoarthritic cartilage. J Rheumatol 16: 646–655PubMedGoogle Scholar
  47. Pelletier JP, Martel-Pelletier J (1989) Evidence for the involvement of interleukin 1 in human osteoarthritic cartilage degradation: protective effect of NSAID. J Rheumatol (Suppl 18 ) 16: 19–27Google Scholar
  48. Verbruggen G, Veys EM, Malfait AM et. al (1989) Proteoglycan metabolism in tissue cultured human articular cartilage. Influence of piroxicam. J Rheumatol 16: 355–362Google Scholar
  49. Verbruggen G, Veys EM, Malfait AM et. al (1990) Proteoglycan metabolism in tissue-cultured human articular cartilage. Scand J Rheumatology 19: 257–268CrossRefGoogle Scholar
  50. Yang XH, Zhang ZX (1991) Effects of DMSO and glycerol in 35S incorporation of articular cartilage. Cryo-Letters 12: 53–58Google Scholar
  51. Adams ME, Billingham MFJ (1982) Animal models of degenerative joint disease. Current Topics in Pathology 71: 265–297PubMedCrossRefGoogle Scholar
  52. Bendele AM, Hulman JF (1988) Spontaneous cartilage degeneration in guinea pigs. Arthr Rheum 31: 561–565CrossRefGoogle Scholar
  53. Burton-Wurster N, Todhunter RJ, Lust G (1993) Animal models of osteoarthritis. In. Woessner JF, Howell DS (eds.) Joint cartilage degradation. Basic and clinical aspects. New York, Marcel Dekker Inc.: 347–384Google Scholar
  54. Carney SL (1991) Cartilage research, biochemical, histologic, and immunohistochemical markers in cartilage, and animal models of osteoarthritis. Current Opinion Rheumatol 3: 669–675CrossRefGoogle Scholar
  55. Colombo C, Butler M, O’Byrne E, Hickman L (1983) A new model of osteoarthritis in rabbits. I: Development of knee joint pathology following lateral meniscectomy and section of the fibular collateral and sesamoid ligaments. Arthr Rheum 26: 875–886Google Scholar
  56. Farkas T, Boyd RD, Schaffler MB, Radin EL, Burr DB (1987) Early vascular changes in rabbit subchondral bone after repetitive impulsive loading. Clin Orthop 30: 259–267Google Scholar
  57. Greenwald RA (1991) Animal models for evaluation of arthritis drugs. Meth Find Clin Pharmacol 13: 75–83Google Scholar
  58. Greenwald RA (1993) Cartilage degradation in animal models of inflammatory joint disease. In: Woessner JF, Howell DS (eds.) Joint cartilage degradation. Basic and clinical aspects. New York, Marcel Dekker Inc.: 385–408Google Scholar
  59. Greenwald RA, Diamond HS eds (1988) CRC Handbook of animal models for the rheumatic diseases CRC press Boca Raton Vol 1Google Scholar
  60. Haakenstad LH (1969) Chronic bone and joint diseases in relation to conformation in the horse. Eq Vet J 1: 248CrossRefGoogle Scholar
  61. Hess EV, Herman JH (1986) Cartilage metabolism and anti- inflammatory drugs in osteoarthritis. Am J Med 81: 36–43PubMedGoogle Scholar
  62. Kalbhen DA (1983) Pharmakologische Beurteilung von Möglichkeiten einer Knorpelschutztherapie bei degenerativen Gelenkerkrankungen (Arthrose). Z Rheumatol 42: 187–194PubMedGoogle Scholar
  63. Kalbhen DA (1987) Chemical model of osteoarthritis — a pharmacological evaluation. J Rheumatol 14: 130–131PubMedGoogle Scholar
  64. Lindenhayn K, Haupt R, Kristan J, Regling G (1984) Proteinase activity in the joint cartilage of sheep following mechanical arthrosis induction using an impulse stress instrument. Beitr Orthop Traumatol 31: 507–511PubMedGoogle Scholar
  65. Lust G, Rendano VT, Summers BA (1985) Canine hip dysplasia: concepts and diagnosis. J Am Vet Med Assoc 187: 638–640PubMedGoogle Scholar
  66. Malemud CJ (1993) Markers of osteoarthritis and cartilage research in animal models. Current Opinion in Rheumatology 5: 494–502PubMedCrossRefGoogle Scholar
  67. Mazières B, Herou P, Dambreville JM, Thiechart H (1984) Die Wirkung eines Glykosaminoglykan-Peptid-Komplexes ( GAG-Peptid-Komplex) bei experimenteller Arthrose am Kaninchen. Akt Rheumatol 9: 133–138Google Scholar
  68. Meacock SCR, Bodmer JL, Billingham MFJ (1990) Experimental osteoarthritis in guinea pigs. J Exp Pathol 71: 279–293Google Scholar
  69. Meyer-Carrive I, Ghosh P (1992) Effects of tiaprofenic acid ( Surgam) on cartilage proteoglycans in the rabbit joint immobilization model. Ann Rheum Dis 51: 448–455Google Scholar
  70. Moskowitz RW (1990) The relevance of animal models in osteoarthritis. Scand J Rheum 81 (Suppl): 21–23CrossRefGoogle Scholar
  71. Moskowitz RW (1992) Experimental models of osteoarthritis. In: Moskowitz RW, Howell DS, Goldberg VM, Mankin HJ (eds.) Osteoarthritis: Diagnosis and medical/surgical management. 2nd ed. Philadelphia: W.B.Saunders. pp 213–232Google Scholar
  72. Moskowitz RW, Davis W, Sammarco J, Martens M, Baker J, Mayor M, Burstein AH, Frankel BH (1973) Experimentally induced degenerative joint lesions following partial menisectomy in the rabbit. Arthr Rheum 16: 397–405CrossRefGoogle Scholar
  73. Moskowitz RW, Howell DS, Goldberg VM, Muniz O, Pita JC (1979) Cartilage proteoglycan alterations in an experimentally induced model of rabbit osteoarthritis. Arthr Rheum 22: 155–163CrossRefGoogle Scholar
  74. Palmoski MJ, Brandt KD (1982) Aspirin aggravates the degeneration of canine joint cartilage caused by immobilization. Arthritis Rheum 25: 1333–1342PubMedCrossRefGoogle Scholar
  75. Pita JC, Manicourt DH, Muller FJ, Howell DS (1986) Studies on the potential reversibility of osteoarthritis in some experimental animal models. In Kuettner KE, Schleyerbach R, Hascall VC eds Articular cartilage biochemistry. Raven Press New York, 349–363Google Scholar
  76. Pritzker KPH (1994) Animal models for Osteoarthritis: Processes, problems, and prospects. Ann Rheum Dis 53: 406–420PubMedCrossRefGoogle Scholar
  77. Pritzker KPH, Chateauvert JM, Grynpas MD, Renlund RC, Turnquist J, Kessler MJ (1989) Rhesus macaques as an experimental model for degenerative arthritis. P R Health Sci J 8: 99–102PubMedGoogle Scholar
  78. Schwartz ER (1985) Surgically induced osteoarthritis in guinea pigs: studies of proteoglycans, collagens, and non-collagen proteins. In: Peyron JG, ed. Osteoarthritis: current clinical and fundamental problems. Proc of a Workshop held in Paris April 9–11, 1984. Rueil-Malmaison: Geigy: 273–288Google Scholar
  79. Todhunter RJ, Lust G (1992) Synovial joint anatomy, biology and pathobiology. In: Auer J, ed. Equine Surgery Philadelphia, Saunders:844–866Google Scholar
  80. Williams JM, Uebelhart D, Ongchi DR, Kuettner KE, Thonar EJMA (1992) Animal models of articular cartilage repair. In: Kuettner KE, Schleyerbach R, Pyron JG, Hascall VC (eds.) Articular cartilage and osteoarthritis. New York Raven Press:511–525Google Scholar
  81. Abatangelo G, Botti P, Del Bue M, Gei G, Samson JC, Cortivo R, DeGalateo A, Martelli M (1989) Intra-articular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. I. Biochemical results. Clin Orthop Rel Res 241: 278–285Google Scholar
  82. Adams ME, Pelletier JP (1988) Canine anterior cruciate ligament transection model of osteoarthritis. In Greenwald RA, Diamond HS (eds) CRC handbook of animal models for the rheumatic diseases CRC press Boca Raton Vol 2: 57–81Google Scholar
  83. Brandt KD, Adams ME (1989) Exuberant repair of articular cartilage damage. Effect of anterior cruciate ligament transection in the dog. Trans Orthop Res Soc 14: 584Google Scholar
  84. Brandt KD, Braunstein EM, Visco DM, O’Connor B. Heck D, Albrecht M (1991) Anterior (cranial) cruciate ligament transection in the dog: A bona fide model of osteoarthritis, not merely of cartilage injury and repair. J Rheumatol 18: 436–446Google Scholar
  85. Brandt KD, Myers SL, Burr D, Albrecht M (1991) Osteoarthritic changes in canine articular cartilage, subchondral bone and synovium 54 months after transection of the anterior cruciate ligament. Arthr Rheum 34: 1560–1570CrossRefGoogle Scholar
  86. Colombo C (1988) Partial lateral meniscectomy with section of fibular collateral and sesamoid ligaments in the rabbit. In Greenwald RA, Diamond HS (eds) CRC handbook of animal models for the rheumatic diseases CRC press Boca Raton Vol 2: 27–55Google Scholar
  87. DiPasquale G, Caputo CB, Crisman JW (1988) Rabbit partial medial meniscectomy. In Greenwald RA, Diamond HS (eds) CRC handbook of animal models for the rheumatic diseases CRC press Boca Raton Vol 2: 19–25Google Scholar
  88. Hannan H, Ghosh P, Bellenger C, Taylor T (1987) Systemic administration of glycosaminoglycan polysulfate (arteparon) provides partial protection of articular cartilage from damage produced by meniscectomy in the canine. J Orthop Res 5: 47–59PubMedCrossRefGoogle Scholar
  89. Johnson RG (1986) Transection of the canine anterior cruciate ligament: a concise review of experience with this model of degenerative joint disease. Exp Pathol 30: 209–213PubMedCrossRefGoogle Scholar
  90. McDevitt C, Gilbertson E, Muir H (1977) An experimental model of osteoarthritis; early morphological and biochemical changes. J Bone Joint Surg 59B: 24–35Google Scholar
  91. Myers SL, Brandt KD, O’Connor BL (1991) Low dose prednisone treatment does not reduce the severity of osteoarthritis in dogs after cruciate ligament transection. J Rheum 18: 1856–1862PubMedGoogle Scholar
  92. Newton CII, Fetter DA, Bashey RI, Jimenez SA (1984) Clinical studies and pathological changes in articular cartilage in experimental canine osteoarthrosis and effects of the in vivo administration of a glycosaminoglycan peptide ( GAGPeptide-complex) from bone marrow and cartilage. Akt Rheumatol 9: 128–132Google Scholar
  93. Pelletier JP, Martel-Pelletier J (1985) Cartilage degradation by neutral proteoglycanases in experimental osteoarthritis: suppression by steroids. Arthr Rheum 28: 1393CrossRefGoogle Scholar
  94. Pelletier JP, Martel-Pelletier J (1991) In vivo protective effects of prophylactic treatment with tiaprofenic acid or intraarticular corticosteroids on osteoarthritic lesions in the experimental dog model. J Rheumatol 18 (Suppl 27): 127–130Google Scholar
  95. Pond MJ, Nuki G (1973) Experimentally-induced osteoarthritis in the dog. Ann Rheum Dis 32: 387PubMedCrossRefGoogle Scholar
  96. Schiavinato A, Lini E, Guidolin D, Pezzoli G, Botti P, Martelli M, Cortivo R, DeGalateo A, Abatangelo G (1989) Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. II. Morphological findings. Clin Orthop Rel Res 241: 286–299Google Scholar
  97. Schwartz E (1988) Surgically induced osteoarthritis in guinea pigs. In Greenwald RA, Diamond HS (eds) CRC handbook of animal models for the rheumatic diseases CRC press Boca Raton Vol 2: 89–95Google Scholar
  98. Vignon E, Arlot M, Hartman D, Moyer B, Ville G (1983) Hypertrophic repair of articular cartilage in experimental osteoarthrosis. Ann Rheum Dis 42: 82–88PubMedCrossRefGoogle Scholar
  99. Chandrasekhar S, Esterman MA, Hoffman HA (1987) Microdetermination of proteoglycans and glycosaminoglycans in the presence of guanidine hydrochloride. Anal Biochem 161: 103–108PubMedCrossRefGoogle Scholar
  100. Farndale RW, Buttle DJ, Barrett AJ (1986) Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethyl-methylene blue. Biochim Biophys Acta 883: 173–177PubMedCrossRefGoogle Scholar
  101. Karbowski A, Raiss RX, Schneider EJ (in prep) Continuous intraarticular therapy using an osmotic minipump Mankin Hi, Dorfman H, Lipiello L (1971) Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips. J Bone Joint Surgery 53A: 523–537Google Scholar
  102. Romeis B (1989) Mikroskopische Technik. 17th ed Urban Schwarzenberg MünchenGoogle Scholar
  103. Rosenberg L (1971) Chemical basis for the histological use of safranin-O in the study of articular cartilage. J Bone Joint Surgery 53A: 69–82Google Scholar
  104. vanderSluijs JA (1992) The reliability of the Mankin score for osteoarthritis. J Orthop Res 10: 58–61CrossRefGoogle Scholar
  105. Williams JM, Downey C, Thonar EJMA (1988) Increase in levels of serum keratan sulfate following cartilage proteoglycan degradation in the rabbit knee joint. Arthr Rheum 31: 557–560CrossRefGoogle Scholar
  106. Williams JM, Ongchi DR, Thonar EJMA (1993) Repair of articular cartilage injury following intra-articular chymopapain-induced matrix proteoglycan loss. J Orthop Res 11: 705–716PubMedCrossRefGoogle Scholar
  107. Benjamin M, Ralphs JR, Archer CW, Mason RM, Chambers M, Dowthwaite GP (1995) Cytoskeletal changes in articular fibrocartilage are an early indicator of osteoarthritis in STR/ORT mice. Orthop Res Soc 20: 246Google Scholar
  108. Dunham J, Chambers MG, Jasani MK, Bitenski L, Chayen J (1989) Quantitative criteria for evaluating the early development of osteoarthritis and the effect of diclofenac sodium. Agents Actions 28: 93–97PubMedCrossRefGoogle Scholar
  109. Nakamura Y (1990) Histochemical and immunohistochemical studies on knee joint cartilage in spontaneous osteoarthritis in C57 black mice. J Tokyo Med Coll 48: 308–319Google Scholar
  110. Pataki A, Graf HP, Witzemann E (1990) Spontaneous osteoarthritis of the knee-joint in C57BL mice receiving chronic oral treatment with NSAID’s or prednisone. Agents Actions 29: 210–217PubMedCrossRefGoogle Scholar
  111. Raiss RX, Bartlett RR, Schleyerbach R (1992) Genetically Induced Mouse Models of Rheumatic Diseases. Effects of Leflunomide on Articular Manifestations. In: Kuettner KE, Schleyerbach R, Pyron JG, Hascall VC (eds.) Articular cartilage and osteoarthritis. New York Raven Press: 712–713Google Scholar
  112. Raiss RX, Caterson B (1992) Immunohistochemical localization of chondroitin sulfate isomers in the knee joint of osteoarthritic mice. In: Kuettner KE, Schleyerbach R, Pyron JG, Hascall VC (eds.) Articular cartilage and osteoarthritis. New York Raven Press:714–715Google Scholar
  113. Schünke M, Tillmann B, Brück M, Müller-Ruchholtz W (1988) Morphologic characteristics of developing osteoarthrotic lesions in the knee cartilage of STR/1N mice. Arthr Rheum 31: 898–905CrossRefGoogle Scholar
  114. Sokoloff L, Crittenden LB, Yamamoto RS, Jay GE (1962) The genetics of degenerative joint disease in mice. Arthr Rheum 5: 531–545CrossRefGoogle Scholar
  115. Walton M (1977) Degenerative joint disease in the mouse knee; histological observations. J Pathol 123: 109–122PubMedCrossRefGoogle Scholar
  116. Walton M (1977) Degenerative joint disease in the mouse knee; radiological and morphological observations. J Pathol 123: 97–107PubMedCrossRefGoogle Scholar
  117. Walton M (1979) Patella displacement and osteoarthrosis of the knee joint in mice. J Pathol 127: 165–172PubMedCrossRefGoogle Scholar
  118. Walton M (1977) Studies of degenerative joint disease in the mouse knee joint; scanning electron microscopy. J Pathol 123: 211–217PubMedCrossRefGoogle Scholar
  119. Wilhelmi G, Maier R (1983) Zur Prüfung potentieller Antiarthrotika an der spontanen Arthrose der Maus. Z Rheumatol 42: 203–205PubMedGoogle Scholar
  120. Bartlett RR, Dimitrijevic M, Mattar T, Zielinski T, Germann T, Rude E, Thoenes G H, Küchle CCA, Schorlemmer HU, Bremer E, Finnegan A, Schleyerbach R (1991). Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of auto-immune disorders and reactions leading to transplantation rejection. Agents and Actions 32: 11–21CrossRefGoogle Scholar
  121. Broide D, Marquardt D, Wasserman S (1986) Effect of nedocromil sodium and sodium cromoglycate on connective tissue and bone marrow derived mast cells: acute and chronic studies. Eur J Respir Dis 69: (Suppl 147): 196–198Google Scholar
  122. Church MK, Young KD (1983) The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine. Br J Pharmacol 78: 671–679PubMedCrossRefGoogle Scholar
  123. Eady RP (1986) The pharmacology of nedocromil sodium. Eur J Respir Dis 69: (Suppl 147): 112–119Google Scholar
  124. Flint KC, Leung KBP, Oearce FL, Hudspith BN, Brostoff J, Johnson N McI (1985) Human mast cells recovered by bronchoalveolar lavage: their morphology, histamine release and the effects of disodium cromoglycate. Clin Sci 68: 427–432Google Scholar
  125. Johnson HG, Bach MK (1975) Prevention of calcium ionophore-induced release of histamine in rat mast cells by disodium cromoglycate. J Immunol 114: 514–516PubMedGoogle Scholar
  126. Johnston RB, Godzik CA, Cohn ZA (1978) Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 148; 115–127PubMedCrossRefGoogle Scholar
  127. Kay AB, Walsh GM, Moqbel R. MacDonald AJ, Nagakura T, Carroll MP, Richerson HB (1987) Disodium cromoglycate inhibits activation of human inflammatory cells in vitro. J Allergy Clin Immunol 80: 1–8PubMedCrossRefGoogle Scholar
  128. Lavens SE, Proud D, Warner JA (1993). A sensitive colorimetric assay for the release of tryptase from human lung mast cells in vitro. J immunol Meth 166: 93–102CrossRefGoogle Scholar
  129. Lawrence ID, Warner JA, Cohan VL, Lichtenstein LM, Kagey-Sobotka A, Vavrek JR, Stewart JM, Proud D (1989) Induction of histamine release from human skin mast cells by bradykinin analogs. Biochem Pharmacol 38: 227–233PubMedCrossRefGoogle Scholar
  130. Otr TSC, Cox JSG (1969) Disodium cromoglycate, an inhibitor of mast cell degranulation and histamine release induced by phospholipase A. Nature 223: 197–198Google Scholar
  131. On TSC, Hall DE, Gwilliam JM, Cox JSG (1971) The effect of sodium cromoglycate on the release of histamine and degranulation of rat mast cells induced by compound 48/80. Life Sci 10: 805–812CrossRefGoogle Scholar
  132. Peretti M, Nuti S, Parente L(1990) Investigation of rat mast cell degranulation using flow cytometry. J Pharmacol Meth 23: 187–194Google Scholar
  133. Riley PA, Mather ME, Keogh RW, Eady RP (1987) Activity of nedocromil sodium in mast-cell-dependent reactions in the rat. Int Arch Allergy Appl Immun 82: 108–110CrossRefGoogle Scholar
  134. Siriganian RP (1976) Histamine release and assay methods for the study of human allergy. In: Rose NR, Friedman H (eds.) Manual of Clinical Immunology, American Society of Microbiology, Washington. pp 603–615Google Scholar
  135. Skolfitsch G, Saria A, Holzer P, Lembeck F (1981) Histamine in tissue: Determination by high-performance liquid chromatography PLC condensation with o-phthalaldehyde. J Chromatogr. 226: 53–59Google Scholar
  136. Wells E, Jackson CG, Harper ST, Mann J, Eady RP (1986) Characterization of primate bronchoalveolar mast cells. II. Inhibition of histamine, LTC4, and PGD2 release from primate bronchoalveolar mast cells and a comparison with rat peritoneal mast cells. J Immunol 137: 3941–3945PubMedGoogle Scholar
  137. Williams PD, Laska DA, Shetler TJ, McGrath JP, White SL, Hoover DM (1991) Vancomycin-induced release of histamine from rat peritoneal mast cells and a rat basophil cell line (RBL-1). Agents Actions 32: 217–223PubMedCrossRefGoogle Scholar
  138. Bartlett RR (1986) Immunopharmacological profile of HWA 486, a novel isoxazol derivative-II. in vivo immunomodulating effects differ from those of cyclophosphamide, prednisolone, or cyclosporin A. Int J Immunpharmacol 8: 199–204CrossRefGoogle Scholar
  139. di Padova FE (1989) Pharmacology of cyclosporine (Sandimmune) V. Pharmacological effects on immune function: in vitro studies. Pharmacol Rev 41: 373–405Google Scholar
  140. Elves MW (1972) The Lymphocytes, Chapter 7, In vitro lymphocyte transformation and antibody formation. Lloyd Luke Ltd. 2nd ed., pp. 381–457Google Scholar
  141. Sensi M, di Mario U, Pozzilli P (1984) Lymphocyte populations. Evaluation of T and B populations, T cell subpopulations and K cells. In: Lamer J, Pohl SL (eds) Methods in Diabetes Research, Vol I: Laboratory Methods, Part B, John Wiley Sons, New York, pp 77–97Google Scholar
  142. Yamamura M, Nikbin B, Hobbs JR (1976) Standardisation of the mixed lymphocyte reaction. J Immunol Meth 10: 367–378CrossRefGoogle Scholar
  143. Zan-Bar I (1983) Modulation of B and T cell subsets in mice treated with fractionated total lymphoid irradiation. I. Blockade of differentiating B cell pathways. Eur J Immunol 13: 35–40PubMedCrossRefGoogle Scholar
  144. Chong ASF, Finnegan A, Jiang XL, Gebel H, Sanitary HN, Foster P, Williams JW (1993) Leflunomide, a novel immunosuppressive agent. Transplantation 55: 1361–1366PubMedCrossRefGoogle Scholar
  145. Chong ASF, Gebel H, Finnegan A, Petraitis EE, Jiang XL, Sankary HN, Foster P, Williams JW (1993) Leflunomide, a novel immunomodulatory agent: In vitro analyses of the mechanism of immuno-suppression. Tranplant Proc 25: 747–749Google Scholar
  146. Clipstone NA, Crabtree GR (1993) Calcineurin is a key signaling enzyme in T lymphocyte activation and the target of the immunosuppressive drugs cyclosporin A and FK506. Ann NY Acad Sci 696: 20–30PubMedCrossRefGoogle Scholar
  147. Dayton JS, Turka LA, Thompson CB, Mitchell BS (1992) Comparison of the effects of mizoribine with those of azathioprine, 6-mercaptopurine, and mycophenolic acid on T lymphocyte proliferation and purine ribonucleotide metabolism. Mol Pharmacol 41: 671–676PubMedGoogle Scholar
  148. di Padova FE (1989) Pharmacology of cyclosporine (Sandimmune) V. Pharmacological effects on immune function: in vitro studies. Pharmacol Rev 41: 373–405Google Scholar
  149. Yamamura M, Nikbin B, Hobbs JR (1976) Standardisation of the mixed lymphocyte reaction. J Immunol Meth 10: 367–378CrossRefGoogle Scholar
  150. Zielinski T, Herrmann M, Müller HJ, Riedel N, Bartlett RR (1994) The influence of leflunomide on cell cycle, IL-2receptor (IL-2-R) and its gene expression. Agents Actions 41, Spec Conf Issue: C204 - C205Google Scholar
  151. Zielinski T, Müller HJ, Bartlett RR (1993) Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers. Agents Actions 38, Spec Conf Issue: C80 - C83Google Scholar
  152. Bartlett RR (1986) Immunopharmacological profile of HWA 486, a novel isoxazol derivative-II. in vivo immunomodulating effects differ from those of cyclophosphamide, prednisolone, or cyclosporin A. Int J Immunpharmacol 8: 199–204CrossRefGoogle Scholar
  153. Bird J, Giroud JP (1985) An appraisal of the technique of polymorphonuclear leukocyte chemiluminescence as a means to detect compounds with antiinflammatory activity. J Pharmacol Meth 14: 305–312CrossRefGoogle Scholar
  154. Johnson Jr RB, Codzik CA, Cohn ZA (1978) Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exper. Med. 148: 115–120Google Scholar
  155. Kurosawa M, Hanawa K, Kobayashi S, Nakano M (1990) Inhibitory effects of azelastine on superoxide anion generation from activated inflammatory cells measured by a simple chemiluminescence method. Arzneim Forsch/Drug Res 40: 767–770Google Scholar
  156. Merétey K, Boehm U, Falus A (1983) Chemiluminescence response of human blood mononuclear cells to PAH and histamine. Agents Actions 13: 237–240PubMedCrossRefGoogle Scholar
  157. Seeds MC, Parce JW, Szeijda P, Bass DA (1985) Independent stimulation of membrane potential changes and the oxidative metabolic burst in polymorphonuclear leukocytes. Blood 65: 233–240PubMedGoogle Scholar
  158. Selvaraj R, Sbarra AJ, Thomas GB, Cetrulo CL, Mitchell GW (1982) A microtechnique for studying chemiluminescence response of phagocytes using whole blood and its application to the evaluation of phagocytes in pregnancy. J Reticutoend Soc 31: 3–16Google Scholar
  159. Weidemann MJ, Smith R, Heaney T, Alaudeen S (1980) On the mechanism of the generation of chemiluminescence by macrophages. Behring Inst. Mitt. 65: 42–54Google Scholar
  160. Weinberg JB, Misokonis MA (1983) Phorbol diester-induced H202 production by peritoneal macrophages. Cell Immun 80: 405–415CrossRefGoogle Scholar
  161. Bartlett RR (1986) Immunopharmacological profile of HWA 486, a novel isoxazol derivative — II. in vivo immunomodulating effects differ from those of cyclophosphamide, prednisolone, or cyclosporin A. Int J Immunpharmacol 8: 199–204CrossRefGoogle Scholar
  162. Bord JF, Feurer C, Gubler HU, Stähelin H (1976) Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions 6: 468–475CrossRefGoogle Scholar
  163. Cunningham AJ, Szenberg A (1968) Further improvements in the plaque technique for detecting single antibody forming cells. Immunology 14: 599–608PubMedGoogle Scholar
  164. Stockinger (1978) Negative Rückkoppelungsmechanismen des Immunsystems. Johannes Gutenberg Universität MainzGoogle Scholar
  165. Zaalberg (1964) A simple method for detecting single antibody-forming cells. Nature 202: 1231PubMedCrossRefGoogle Scholar
  166. Barthold DR, Kysela S, Steinberg AD (1974) Decline in suppressor T cell function with age in female NZB mice. J Immunol 112: 9PubMedGoogle Scholar
  167. Bielschowski M, Helyer BJ, Howie JB (1959) Spontaneous anemia in mice of the NZB/BL strain. Proc Univ Otago Med School 37: 9–11Google Scholar
  168. Blanchard D, Bach MA (1980) Thymic function in NZB mice. Clin Exp Immunol 42: 1–9PubMedGoogle Scholar
  169. Cole RK (1966) Hereditary hypothyroidism in domestic fowl. Genetics 13: 1021–1033Google Scholar
  170. Cole RK, Kite JH, Wick G, Witebsky E (1970) Inherited autoimmune thyroiditis in the fowl. Poultry Sci 49: 480–488Google Scholar
  171. Cole RK, Kite JH, Witebsky E (1968) Hereditary autoimmune thyroiditis in the fowl. Science 160: 1357–1358PubMedCrossRefGoogle Scholar
  172. Field JB (ed) (1983) The juvenile diabetes foundation workshop on the spontaneously diabetic BB rat: its potential for insight into human juvenile diabetes. Metabolism 32 (Suppl 1)Google Scholar
  173. Helyer BW, Howie JB (1963) Renal disease associated with positive lupus erythematosus test in a cross-bred strain of mice. Nature 197: 197PubMedCrossRefGoogle Scholar
  174. Howie JB, Helyer BJ (1968) The immunology and pathology of NZB mice. In: Advances in Immunology. New York, Academic Press, 9: 215–266Google Scholar
  175. Kessler HS (1968) A laboratory model for Sjögren’s syndrome. Am J Pathol 52: 671–685PubMedGoogle Scholar
  176. Leiter EH, Prochazka M, Coleman DL (1987) Animal model of human disease. The non-obese diabetic ( NOD) mouse. Am J Pathol 128: 380–383Google Scholar
  177. Like AA, Butler L, Williams RM, Appel MC, Weringer EJ, Rossini AA (1982) Spontaneous autoimmune diabetes mellitus in the BB rat. Diabetes 31 (Suppl) 7–13PubMedCrossRefGoogle Scholar
  178. Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980) Breeding of a non-obese, diabetic strain of mice. Exp Anim 29: 1–13Google Scholar
  179. Miyazaki A, Hanafusa T, Yamada K, Miyagawa J, FujinoKurihara H, Nagajima H, Nonaka K, Tarui S (1985) Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study. Clin Exp Immunol 60: 622–630PubMedGoogle Scholar
  180. Schuurs AHWM, Verheul HAM, Wick G (1989) Spontaneous autoimmune models. Pharmacological Methods in the Control of Inflammation. pp 449–485, Alan R. Liss, IncGoogle Scholar
  181. van Tienhoven A, Cole RK (1962) Endocrine disturbance in obese chickens. Anat Rev 142: 111–122CrossRefGoogle Scholar
  182. Wick G, Sundick RS, Albini B (1974) The obese strain (OS) of chickens: an animal model with spontaneous autoimmune thyroiditis. Clin Immunol Immunopathol 3: 272–300PubMedCrossRefGoogle Scholar
  183. Yale JF, Marliss EB (1984) Altered immunity and diabetes in the BB rat. Clin Exp Immunol 57: 1–11PubMedGoogle Scholar
  184. Austen KF, Brocklehurst WE (1961) Anaphylaxis in chopped guinea pig lung. J Exp Med 113: 521–537PubMedCrossRefGoogle Scholar
  185. Bhattacharya BK, Delaunois AL (1955) An improved method for the perfusion of isolated lung of guinea pig. Arch Int Pharmacodyn 101: 495–510PubMedGoogle Scholar
  186. Davies GE, Evans (1973) Studies with two new phosphodiesterase inhibitors (ICI 58,301 and ICI 63,197) on anaphylaxis in guinea pigs, mice and rats. Int Arch Allergy 45: 467–478Google Scholar
  187. Elwood W, Lötvall JO, Barnes PJ, Chung KF(1992) Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitized Brown-Norway rats. Am Rev Resp Dis 145: 1289–1294Google Scholar
  188. Omote M, Sakai K, Mizusawa H (1994) Acute effects of deflazacort and its metabolite 21-desacetyl-deflezacort on allergic reactions. Arzneim Forsch/Drug Res 44: 149–153Google Scholar
  189. Ufkes JGR, Ottenhof M (1984) Characterization of various antiallergic agents using a new method for inducing systemic anaphylaxis in the rat. J Pharmacol Meth 11: 219–226CrossRefGoogle Scholar
  190. Anderson P, Brattsand R (1982) Protective effects of the glucocorticoid, budesonide, on lung anaphylaxis in actively sensitized guinea pigs: Inhibition of the IgE — but not of the IgG — mediated anaphylaxis. Br J Pharmacol 76: 139–147Google Scholar
  191. Austen KF, Brocklehurst WE (1961) Anaphylaxis in chopped guinea pig lung. I. Effect of peptidase substrates and inhibitors. J Exper Med 113: 521–537Google Scholar
  192. Dale HH (1913) The anaphylactic reaction of plain muscle in the guinea-pig. J Pharmacol Exper Ther 4: 167–223Google Scholar
  193. Koppel GA, Haisch KD, Spaethe SM, Schmidtke JR, Fleisch JH (1981) Schultz-Dale reaction in mouse trachea. J Pharmacol Meth 6: 39–43CrossRefGoogle Scholar
  194. Laekeman GM, Herman AG, van Nueten JM (1977) Influence of different drugs on the slow response of the intestine during the Schultz-Dale reaction. Arch Int Pharmacodyn 230: 335PubMedGoogle Scholar
  195. Omote M, Sakai K, Mizusawa H (1994) Acute effects of deflazacort and its metabolite 21-desacetyl-deflezacort on allergic reactions. Arzneim Forsch/Drug Res 44: 149–153Google Scholar
  196. Schultz WH (1910) Physiological studies in anaphylaxis. 1. The reaction of smooth muscle of the guinea-pig sensitized with horse serum. J Pharmacol Exper Ther 1: 549–567Google Scholar
  197. Goose J, Blair AMJN (1969) Passive cutaneous anaphylaxis in the rat, induced with two homologous reagin-like antibodies and its specific inhibition with disodium cromoglycate. Immunology 16: 749–760PubMedGoogle Scholar
  198. Griesbacher T, Lembeck F (1987) Actions of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle of the rabbit. Br J Pharmacol 92: 333–340PubMedCrossRefGoogle Scholar
  199. Katayama S, Shionoya H, Ohtake S (1975) A new simple method for extraction of extravasated dye in the skin. Japan J Pharmacol Suppl 25: 103 PGoogle Scholar
  200. Patterson R, Talbot CH, Brandfonbrener M (1971) The use of IgE mediated responses as a pharmacologic test system. The effect of disodium cromoglycate in respiratory and cutaneous reactions and in the electrocardiograms of rhesus monkeys. Int Arch Allergy 41: 592–603Google Scholar
  201. Saria A, Lundberg JM, Skofitsch G, Leznbeck F (1983) Vascular protein leakage in various tissues induced by substance P, capsaicin, bradykinin, histamine and by antigen challenge. Naunyn Schmiedeberg’s Arch Pharmacol 324: 212–218PubMedCrossRefGoogle Scholar
  202. Watanabe N, Ovary Z (1977) Antigen and antibody detection by in vivo methods: a reevaluation of passive cutaneous anaphylactic reactions. J Immunol Meth 14: 381–390CrossRefGoogle Scholar
  203. Bartlett RR, Gebert U, v.Kerékjdrtô B, Schleyerbach R, Thor-wart W, Weitmann KU (1989) Substituted 3-phenyl-7Hthiazolo(3,2-b)(1,2,4)triazin-7-ones as antiinflammatory agents with immunomodulating properties. Drugs Exp Clin Res 15: 521–526Google Scholar
  204. Horvat J, Vidic B, Kosec D, Stojic Z, Jankovic BD (1990) Suppression of Arthus and delayed hypersensitivity reactions to bovine serum albumin by dopaminergic antagonists. Period Biol 92: 81–82Google Scholar
  205. Kamei C, Izushi K, Adachi Y, Shimazawa M, Tasaka K (1991) Inhibitory effect of epinastine on the type II—IV allergic reactions in mice, rats and guinea pigs. Arzneim Forsch/Drug Res 41: 1150–1153Google Scholar
  206. Nagakawa Y, Ogawa T, Kobayashi M, Wagatsuma K, Munakata H, Umezu K, Sato S, Shibata Y, Inoue K, Ishida N (1990) Immunopharmacological studies of 4-acetylaminophenylacetic acid. (MS-932),Int J Immunother 6: 131–140Google Scholar
  207. Omote M, Sakai K, Mizusawa H (1994) Acute effects of deflazacort and its metabolite 21-desacetyl-deflezacort on allergic reactions. Arzneim Forsch/Drug Res 44: 149–153Google Scholar
  208. Borel JF (1989) Pharmacology of cyclosporine (Sandimmune) IV. Pharmacological properties in vivo. Pharmacol Rev 41: 259–371Google Scholar
  209. Borel JF, Feurer C, Magnée C, Stähelin H (1977) Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology 32: 1017–1025PubMedGoogle Scholar
  210. Herrmann P, Schreier MH, Borel JF, Feurer C (1988) Mast cell degranulation as a major event in the effector phase of delayed-type hypersensitivity induced by cloned helper cells. Int Arch Allergy Appl Immunol 86: 102–105PubMedCrossRefGoogle Scholar
  211. Kamei C, Izushi K, Adachi Y, Shimazawa M, Tasaka K (1991) Inhibitory effect of epinastine on the type II—IV allergic reactions in mice, rats and guinea pigs. Arzneim Forsch/Drug Res 41: 1150–1153Google Scholar
  212. Mizukoshi S, Tsukamoto M, Tanaka H, Nakamura K, Kato F (1994) Antiinflammatory and immunosuppressive effects of I,6-anhydro-3,4-dideoxy-2-furfuryl-3-D-rhreo-3-enopyranose (MT 2221), a novel anhydro-enopyranose derivative, on experimental animal models. Biol Pharm Bull 17: 1070–1074PubMedCrossRefGoogle Scholar
  213. Nagakawa Y, Ogawa T, Kobayashi M, Wagatsuma K, Munakata H, Umezu K, Sato S, Shibata Y, Inoue K, Ishida N (1990) Immunopharmacological studies of 4-acetylaminophenylacetic acid. (MS-932). Int J Immunother 6: 131–140Google Scholar
  214. Titus RG, Chiller JM (1981) A simple and effective method to assess murine delayed type hypersensitivity to proteins. J Immunol Meth 45: 65–78CrossRefGoogle Scholar
  215. Berkenkopf JW, Marinari LR, Weichman BM (1991) Phospholipase A2 acyl-hydrolytic activity in rat RPAR-induced pleurisy. Agents Actions 34: 93–96PubMedCrossRefGoogle Scholar
  216. Berkenkopf JW, Weichman BM (1991) Comparison of several new 5-lipoxygenase inhibitors in a rat Arthus pleurisy model. Eur J Pharmacol 193: 29–34PubMedCrossRefGoogle Scholar
  217. Burch RM, Connor JR, Bator JM, Weitzberg M, Laemont K, Noronha-Blob L, Sullivan JP, Steranka LR (1992) NPC 15669 inhibits the reverse passive Arthus reaction in rats by blocking neutrophil recruitment. J Pharm Exp Ther 263: 933–937Google Scholar
  218. Camussi G, Tetta C, Bussolino F, Baglioni C (1990) Antiinflammatory peptides (antiflammins) inhibit synthesis of platelet-activating factor, neutrophil aggregation and chemotaxis, and intradermal inflammatory reactions. J Exp Med 171: 913–927PubMedCrossRefGoogle Scholar
  219. Carter GW, Young PR, Albert DH, Bouska J, Dyer R, Bell RL, Summers JB, Brooks DW (1991) 5-Lipoxygenase inhibitory activity of Zileuton. J Pharm Exp Ther 256: 929–937Google Scholar
  220. Chang YH, Otterness IG (1981) Effects of pharmacologic agents on the reversed passive Arthus reaction in the rat. Eur J Pharmacol 69: 155–164PubMedCrossRefGoogle Scholar
  221. Humphrey JH (1955 a) The mechanism of Arthus reactions. I. The role of polymorphonuclear leukocytes and other factors in reversed passive Arthus reactions in rabbits. Br J Exp Pathol 36: 268–282Google Scholar
  222. Humphrey JH (1955 b) The mechanism of Arthus reactions. I1. The role of polymorphonuclear leukocytes and platelets in reversed passive Arthus reactions in the guinea-pig. Br J Exp Pathol 36: 283–289Google Scholar
  223. Kim KH, Martin IC, Young PR, Carter GW, Haviv F (1990) Inhibitors of immune complex-induced inflammation: 5-substituted 3-[1-(2-benzoxazolyl)hydrazino]propanenitrile derivatives. J Pharm Sci 79: 682–684PubMedCrossRefGoogle Scholar
  224. Okamoto H, Iwahisa Y, Terawasa M (1992) Suppression of the Arthus reaction by Y-24180, a potent and specific antagonist of platelet-activating factor. Agents Actions 35: 149–158PubMedCrossRefGoogle Scholar
  225. Ting PC, Kaminski JJ, Sherlok MH, Tom WC, Lee JF, Bryant RW, Watnick AD, McPhail AT (1990) Substituted 1,3dihydro-2H-pyrrolo[2,3-b]pyridin-2-ones as potential anti-inflammatory agents. J Med Chem 33: 2697–2706PubMedCrossRefGoogle Scholar
  226. Yamamoto S, Dunn CD, Deporter DA, Capasso F, Willoughby DA, Huskisson EC (1975) A model for the quantitative study of Arthus (immunologic) hypersensitivity in rats. Agents Actions 5: 374–377PubMedCrossRefGoogle Scholar
  227. Bartlett RR, Schleyerbach R (1985) Immunopharmacological profile of a novel isoxazol derivative, HWA 486, with potential antirheumatic activity. I. Disease modifying action on adjuvant arthritis of the rat, Int J Immunopharmacol 7: 7–18Google Scholar
  228. Beck FWJ, Whitehouse MW, Pearson CM (1974) Drug sensitivity of rat adjuvant arthritis, induced with `adjuvants’ containing no mineral oil components. Proc Soc Exp Biol Med 146: 665–669PubMedGoogle Scholar
  229. Brackertz D, Mitchell GF, MacKay IR (1977) Antigen-induced arthritis in mice. Arthr Rheum 20: 841–850CrossRefGoogle Scholar
  230. Colpaert FC (1987) Evidence that adjuvant arthritis in the rat is associated with chronic pain. Pain 28: 201–222PubMedCrossRefGoogle Scholar
  231. Connolly KM, Stecher VJ, Danis E, Pruden DJ, LaBrie T (1988) Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin-A or methotrexate. Int J Immunopharmac 10: 717–728CrossRefGoogle Scholar
  232. Crossley MJ, Holland T, Spowage M, Hunneyball IM (1989) Monarticular antigen-induced arthritis in rabbits and mice. In: Pharmacological Methods in the Control of Inflammation. Alan R Liss, Inc., pp 415–439Google Scholar
  233. Cruwys SC, Garrett NE, Perkins MN. Blake DR, Kidd BL (1994) The role of bradykinin B1 receptors in the maintenance of intra-articular plasma extravasation in chronic antigen-induced arthritis. Br J Pharmacol 113: 940–944PubMedCrossRefGoogle Scholar
  234. del Pozo E, Graeber M, Payne T (1990) Regression of bone and cartilage loss in adjuvant arthritic rats after treatment with cyclosporin A. Arthr Rheum 33: 247–252CrossRefGoogle Scholar
  235. Gardner DL (1960) The experimental production of arthritis. A review. Ann rheum Dis 19: 297–317PubMedCrossRefGoogle Scholar
  236. Kazuna S, Kawai K (1975) Evaluation of analgesic agents in rats with adjuvant arthritis. Chem Pharm Bull (Tokyo) 23: 1184–1191CrossRefGoogle Scholar
  237. Leisten JC, Gaarde WA, Scholz W (1990) Interleukin-6 serum levels correlate with footpad swelling in adjuvant-induced arthritic Lewis rats treated with cyclosporin A or indomethacin. Clin Innnunol Immunopathol 56: 108–115CrossRefGoogle Scholar
  238. Mohr W, Wild A (1976) Adjuvant arthritis. Arzneim Forsch/ Drug Res 26: 1860–1866Google Scholar
  239. Pearson CM (1956) Development of’ arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exper Biol Med. 91: 95–101Google Scholar
  240. Pearson CM (1963) Experimental joint disease. Observations on adjuvant-induced arthritis. J Chron Dis 16: 863–874.PubMedCrossRefGoogle Scholar
  241. Pearson CM, Wood FD (1959) Studies on polyarthritis and other lesions induced in rats by injection of mycobacterium adjuvant. I. General clinic and pathological characteristics and some modifying factors. Arthr Rheum 2: 440–459Google Scholar
  242. Perper RJ, Alvarez B, Colombo C, Schroder H (1971) The use of a standardized adjuvant arthritis assay to differentiate between anti-inflammatory and immunosuppressive agents. Proc Soc Exp Biol Med 137: 506–512Google Scholar
  243. Pircio AW, Fedele CT, Bierwagen ME (1975) A new method for the evaluation of analgesic activity using adjuvant-induced arthritis in the rat. Eur J Pharmacol 31: 207–215PubMedCrossRefGoogle Scholar
  244. Rooks WH, Tomolonis AJ, Maloney PJ, Wallach MB, Schuler ME (1982) The analgesic and anti-inflammatory profile of (±)-5-benzoyl-1,2-dihydro-3H-pyrrolo[I,2a]pyrrole-1carboxylic acid (RS-37619). Agents Actions 12: 684–690PubMedCrossRefGoogle Scholar
  245. Sandow J, Alpermann H, Metzger H, Vogel HG (1971) ct-2Glycoprotein levels in the experimental immunoarthritis of the rat. Naunyn-Schmiedeberg’s Arch Pharmacol 269: 483Google Scholar
  246. Schorlemmer HU, Dickneite G (1992) Preclinical studies with 15-deoxyspergualin in various animal models for autoimmune diseases. Ann NY Acad Sci 685: 155–174CrossRefGoogle Scholar
  247. Tsurumi K, Kokuba S, Okada K, Yanagihara M, Fujimura H (1986) Pharmacological investigations of the new antiinflammatory agent 2-(10,1 1-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 4th communication:Inhibitory effects on rat adjuvant arthritis. Arzneim-Forsch/Drug Res 36: 1810–1817Google Scholar
  248. Walz DT, DiMartino MJ, Kuch JH, Zuccarello W (1969) Adjuvant-induced arthritis in rats — Temporal relationship of drug effects on physiological, biochemical, and haematological parameters. Pharmacologist 11: 266Google Scholar
  249. Weichman BM (1989) Rat adjuvant arthritis: A model of chronic inflammation. In: Pharmacological Methods in the Control of Inflammation. Alan R Liss, Inc., pp 363–380Google Scholar
  250. Wilder RL, Allen JB, Hansen C (1987) Thymus-dependent and -independent regulation of la antigen expression in situ by cells in the synovium of rats with streptococcal cell wall-induced arthritis, J Clin Invest 79: 1160–1171PubMedCrossRefGoogle Scholar
  251. Wilder RL, Calandra GB, Garvin AJ, Wright KD, Hansen CT (1982) Strain and sex variation in the susceptibility to streptococcal wall-induced polyarthritis in the rat. Arthritis Rheum 25: 1064–1072PubMedCrossRefGoogle Scholar
  252. Yocum DE, Allen JB, Wahl SM, Calandra GB, Wilder RL (1986) Inhibition by cyclosporin A of streptococcal wall-induced arthritis and hepatic granulomas in rats. Arthritis Rheum 29: 262–273PubMedCrossRefGoogle Scholar
  253. Cannon GW, McCall S, Cole BC, Griffiths MM, Radov LA, Ward JR (1990) Effects of indomethacin, cyclosporin, cyclophosphamide, and placebo on collagen-induced arthritis of mice. Agents Actions 29: 315–323PubMedCrossRefGoogle Scholar
  254. Carlson RP, Baeder WL, Caccese RG, Warner LM, Sehgal SN (1992) Effects of orally administered rapamycin in animal models of arthritis and other autoimmune diseases. Ann NY Acad Sci 685: 86–113CrossRefGoogle Scholar
  255. Henderson H, Staines NA, Burrai I, Cox JH (1984) The anti-arthritic and immunosuppressive effects of cyclosporine on arthritis induced in the rat by type II collagen. Clin Exp Immunol 57: 51–56PubMedGoogle Scholar
  256. Horn JT, Butler LD, Riedl PE, Bendele AM (1988) The progression of the inflammation in established collagen-induced arthritis can be altered by treatments with immunological or pharmacological agents which inhibit T cell activities. Eur J Immunol 18: 881–888CrossRefGoogle Scholar
  257. Kaibara N, Hotokebuchi T, Takagishi K, Katsuki I (1983) Paradoxical effects of cyclosporin A on collagen arthritis in rats. J Exp Med 158: 2007–2015PubMedCrossRefGoogle Scholar
  258. Nemoto K, Mae T, Abe F, Takeuchi T (1992) Successful treatment with a novel immunosuppressive agent, deoxyspergualin, in type II collagen-induced arthritis in mice. Ann NY Acad Sci 685: 148–154CrossRefGoogle Scholar
  259. Phadke K, Carroll J, Nanda S (1982) Effects of various anti-inflammatory drugs on type II collagen-induced arthritis in rats. Clin Exp Immunol 47: 579–586PubMedGoogle Scholar
  260. Probeert AW, Schrier DJ, Gilbertsen RB (1984) Effects of antiarthritic compounds on type II collagen-induced arthritis in rats. Arch Int Pharmacodyn 269: 167–176Google Scholar
  261. Takagishi K, Kaibara N, Hotokebuchi T, Arita C, Morinaga M, Arai K (1986) Effects of cyclosporin on collagen induced arthritis in mice. Ann Rheum Dis 45: 339–344PubMedCrossRefGoogle Scholar
  262. Takagishi K, Yamamoto M, Miyahara H, Hotokebuchi T, Kaibara N (1992) Comparative study of effects of cyclosporins A and G on collagen arthritis in mice. Agents Actions 37: 284–289PubMedCrossRefGoogle Scholar
  263. Tanaka K, Shimotori T, Makino S, Aikawa Y, Inaba T, Yoshida C, Takano S (1992) Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-l-benzopyran-4-one. 1st Communication: antiinflammatory, analgesic and other related properties. Arzneim Forsch/Drug Res 42: 935–944Google Scholar
  264. Trentham DE, Dynesius-Trentham RA (1989) Type II collagen-induced arthritis in the rat. In: Pharmacological Methods in the Control of Inflammation. Alan R. Liss, Inc., pp 395–413Google Scholar
  265. Trentham DE, Townes AS, Kang AH (1977) Autoimmunity to type II collagen: an experimental model of arthritis. J Exper Med 146: 857–868CrossRefGoogle Scholar
  266. Giant TT, Mikecz K, Arzoumanian A, Poole AR (1987)Google Scholar
  267. ProGiant et al (1987, 1992), Mikecz et al (1987, 1990), teoglycan-induced arthritis in BALB/c mice: Clinical feaGoogle Scholar
  268. Poole (1989) described a proteoglycan-induced pro- tures and histopathology. Arthritis Rheum 30:201–212Google Scholar
  269. Stimpson and Schwab (1989) described a chronic remittent erosive arthritis in rats induced by bacterial peptidoglycan-polysaccharide structures.Google Scholar
  270. Giant TT, Mikecz K, Bartlett RR, Deâk F, Thonar EJMA, Wil- liams JM, Mattar T, Kuettner KE, Schleyerbach R (1992) Immunomodulation of proteoglycan-induced progressive po- lyarthritis by leflunomide. Immunopharmacology 23: 105–116CrossRefGoogle Scholar
  271. Hascall VC, Heinegârd D (1974) Aggregation of proteoglycans. I. The role of hyaluronic acid. J Biol Chem 249: 4232–4241Google Scholar
  272. Heinegâard D (1972) Extraction, fractionation and characterization of proteoglycans from bovine tracheal cartilage. Biochim Biophys Acta 285: 181–192CrossRefGoogle Scholar
  273. Mikecz K, Giant TT, Bukds E, Poole AR (1990) Proteoglycaninduced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice. Arthritis Rheum 33: 866–876PubMedCrossRefGoogle Scholar
  274. Mikecz K, Giant TT, Poole AR (1987) Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum 30: 306–318PubMedCrossRefGoogle Scholar
  275. Poole AR (1989) Cartilage proteoglycan-induced arthritis: a combined model for rheumatoid arthritis and ankylosing spondylitis. In: Pharmacological Methods in the Control of Inflammation. pp 441–447, Alan R. Liss, IncGoogle Scholar
  276. Stimpson AS, Schwab JH (1989) Chronic remittent erosive arthritis induced by bacterial peptidoglycan-polysaccharide structures. In: Pharmacological Methods in the Control of Inflammation. pp 381–394, Alan R. Liss, IncGoogle Scholar
  277. Fournier C, Gepner P, Saouk M, Charreire J (1990) In vivo beneficial effects of cyclosporin A and 1,25-dihydroxyvitamin D3 on the induction of experimental autoimmune thyroiditis. Clin Immunol Immunopathol 54: 53–63PubMedCrossRefGoogle Scholar
  278. Hassman RA, Dieguez C, Rennie DP, Weetman AP, Hall R, McGregor AM (1985) The influence of cyclosporin A on the induction of experimental autoimmune thyroid disease in the PVG/c rat. Clin Exp Immunol 59: 10–16PubMedGoogle Scholar
  279. McGregor AM, Rennie PD, Weetman AP, Hassman RA, Foord SM, Dieguez C, Hall R (1983) The influence of cyclosporin A on experimental autoimmune thyroid disease in the rat. Life Sci 32: 97–108PubMedCrossRefGoogle Scholar
  280. Penhale WJ, Farmer A, Irvine WJ (1975) Thyroiditis in T cell-depleted rats: influence of strain, radiation dose, adjuvants and antilymphocyte serum. Clin Exp Immunol 21: 362–375PubMedGoogle Scholar
  281. Salamero J, Remy JJ, Michel-Béchet M, Chareire J (1987) Experimental autoimmune thyroiditis induced by a 5–10 kDa cryptic fragment from porcine thyroglobin. Eur J Immunol 17: 843–848PubMedCrossRefGoogle Scholar
  282. Tamura K, Woo J, Murase N, Nalesnik M, Thomson AW (1993) Inhibitory effect of FK 506 on autoimmune thyroid disease in the PVG rat. Ann NY Acad Sci 696: 257–262PubMedCrossRefGoogle Scholar
  283. Vladutiu AO (1983) Effect of cyclosporine on experimental autoimmune thyroiditis in mice. Transplantation 35: 518–520PubMedCrossRefGoogle Scholar
  284. Vladutiu AO, Rose NR (1971) Autoimmune murine thyroiditis relation to histocompatibility (H-2) type. Science 174: 1137–1139PubMedCrossRefGoogle Scholar
  285. Estrin M, Herzum M, Buie C, Huber SA (1987) Immunosuppressives in murine myocarditis. Eur Heart J 8 (Suppl J) 259–262CrossRefGoogle Scholar
  286. Estrin M, Huber SA (1987) Coxsackie virus B3-induced myocarditis. Autoimmunity is L3T4’ T helper cell and IL-2 independent in Balb/c mice. Am J Pathol 127: 337–341Google Scholar
  287. Estrin M, Smith C, Huber S (1986) Coxsackie virus B-3 myocarditis. T-cell autoimmunity to heart antigens is resistant to cyclosporin-A treatment. Am J Pathol 125: 244–251Google Scholar
  288. Huber SA, Lodge PA (1984) Coxsackie virus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens. Am J Pathol 116: 21–29Google Scholar
  289. Huber SA, Lodge PA (1986) Coxsackie virus B-3 myocarditis. Identification of different pathogenic mechanisms in DBA/2 and Balb/c mice. Am J Pathol 122: 284–291PubMedGoogle Scholar
  290. Monrad ES, Matsumori A, Murphy JC, Fox JG, Crumpacker CS, Abelmann WH (1986) Therapy with cyclosporine in experimental murine myocarditis with encephalomyocarditis virus. Circulation 7: 1058–1064CrossRefGoogle Scholar
  291. O’Connell JB, Reap EA, Robinson JA (1986) The effects of cyclosporine on acute murine Coxsackie B-3 myocarditis. Circulation 73: 353–359PubMedCrossRefGoogle Scholar
  292. Alvord EC (1984) The challenge: how good a model of MS is EAE today? In: Alvord EC, Kies MW, Suckling AJ (eds) Experimental allergic encephalomyelitis: a useful model for multiple sclerosis. Alan R Liss, New York, pp 3–5Google Scholar
  293. Arnon R (1981) Experimental allergic encephalomyelitis —Susceptibility and suppression. Immunol Rev 55: 5–30PubMedCrossRefGoogle Scholar
  294. Ben-Nun A, Cohen IR (1982) Experimental autoimmune encephalomyelitis (EAE) mediated by T cell lines: process of selection of lines and characterization of the cells. J Immunol 129: 303–308PubMedGoogle Scholar
  295. Bolton C, Borel JF, Cuzner ML, Davison AN, Turner AM (1982) Immunosuppression by cyclosporin A of experimental allergic encephalomyelitis. J Neur Sci 56: 147–153CrossRefGoogle Scholar
  296. Carlson RP, Baeder WL, Caccese RG, Warner LM, Sehgal SN (1992) Effects of orally administered rapamycin in animal models of arthritis and other autoimmune diseases. Ann NY Acad Sci 685: 86–113CrossRefGoogle Scholar
  297. Carlson RP, Hartman DA, Tomchek LA, Walter TL, Lugay JR, Calhoun W, Sehgal SN, Chang JY (1993) Rapamycin, a potential disease-modifying antiarthritic drug. J Pharmacol Exp Ther 266: 1125–1138PubMedGoogle Scholar
  298. Chabannes D, Ryffel B, Borel JF (1992) SRI 62–834, a cyclic ether analogue of the phospholipid ET-18-OCH3, displays long-lasting beneficial effects in chronic relapsing encephalomyelitis in the Lewis rat. Comparison with cyclosporin and (Va12)-dihydrocyclosporin effects in clinical, functional and histological studies. J Autoimmun 5: 199–21 IGoogle Scholar
  299. Feurer C, Chow LH, Borel JF (1988) Preventive and therapeutic effects of cyclosporin and valine2-dihydro-cyclosporin in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Immunol 63: 219–223Google Scholar
  300. Hartung HP, Schäfer B, Fierz W, Heininger K, Toyka KV (1987) Cyclosporin A prevents P2 T cell line-mediated experimental autoimmune neuritis ( AT-EAN) in rat. Neurosci Lett 83: 195–200Google Scholar
  301. Hinrichs DJ, Wegmann KW, Peters BA (1983) The influence of cyclosporin A on the development of actively induced and passively transferred experimental allergic encephalomyelitis. Cell Immunol 77: 202–209PubMedCrossRefGoogle Scholar
  302. King RHM, Craggs RI, Gross MLP, Tompkins C, Thomas PK (1983) Suppression of experimental allergic neuritis by cyclosporin A. Acta Neuropathol (Berl) 59: 262–268CrossRefGoogle Scholar
  303. Levine S, Sowinski R (1977) Suppression of the hyperacute form of experimental allergic encephalomyelitis by drugs. Arch Int Pharmacodyn 230: 309–318PubMedGoogle Scholar
  304. McCombe PA, van der Kreek SA, Pender MP (1990) The effects of prophylactic cyclosporin A on experimental allergic neuritis (EAN) in the Lewis rat. Induction of relapsing EAN using low dose of cyclosporin A. J Neuroimmunol 28: 131–140Google Scholar
  305. McFarlin DF, Blank SE, Kibler RF, McKneally S, Shapira R (1973) Experimental allergic encephalomyelitis in the rat: response to encephalitogenic proteins and peptides. Science 179: 478–483PubMedCrossRefGoogle Scholar
  306. Nakayasu H, Ota K, Tanaka H, Irie H, Takahashi H (1990) Suppression of actively induced and passively transferred experimental allergic neuritis by cyclosporin A. J Neuroimmunol 26: 219–227PubMedCrossRefGoogle Scholar
  307. Polman CH, Matthaei I, de Groot CJA, Koetsier JC, Sminia T, Dijkstra CD (1988) Low-dose cyclosporin A induces relapsing remitting experimental allergic encephalomyelits in the Lewis rat. J Neuroimmunol 17: 209–216PubMedCrossRefGoogle Scholar
  308. Rivers TM, Sprunt DH, Berry GP (1933) Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J Exper Med 58: 39–53CrossRefGoogle Scholar
  309. Rosenthale ME, Datko LJ, Kassarich J, Schneider F (1969) Chemotherapy of experimental allergic encephalomyelitis (EAE) Arch Int Pharmacodyn 179: 251–275PubMedGoogle Scholar
  310. Schuller-Levis GB, Kozlowski PB, Wisniewski HM (1986) Cyclosporin A treatment of an induced attack in a chronic relapsing model of experimental allergic encephalomyelitis. Clin Immunol Immunopathol 40: 244–252PubMedCrossRefGoogle Scholar
  311. Waksman BH, Adams RD (1955) Allergic neuritis: an experimental disease of rabbits induced by the injection of peripheral nervous tissue and adjuvants. J Exp Med 102: 213–234PubMedCrossRefGoogle Scholar
  312. Waksman BH, Adams RD (1956) A comparative study of experimental allergic neuritis in rabbit, guinea-pig and mouse. J Neuropathol Exp Neurol 15: 293–374PubMedCrossRefGoogle Scholar
  313. Bartlett RR, Anagnostopulos H, Zielinski T, Mattar T, Schleyerbach R (1993). Effects of leflunomide on immune responses and models of inflammation. Springer Semin Immunopathol 14: 381–394PubMedCrossRefGoogle Scholar
  314. Bartlett RR, Dimitrijevic M, Mattar T, Zielinski T, Germann T, Riide E, Thoenes G H, Küchle CCA, Schorlemmer HU, Bremer E, Finnegan A, Schleyerbach R (1991). Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of auto-immune disorders and reactions leading to transplantation rejection. Agents and Actions 32: 11–21CrossRefGoogle Scholar
  315. Küchle CCA, Thoenes GH, Langer KH, Schorlemmer HU, Bartlett RR, Schleyerbach R (1991). Prevention of kidney and skin graft rejection in rats by leflunomide, a new immunomodulating agent. Transplant Proc 23: 1083–1086PubMedGoogle Scholar
  316. Mrowka C, Thoenes GH, Langer KH, Bartlett RR (1994) Prevention of acute graft versus host disease ( GVHD) in rats by the immunomodulating drug leflunomide. Ann Hematology 68: 195–199Google Scholar
  317. Murase N, Demetris AJ, Woo J, Tanabe M, Furuya T, Todo S, Starzl TE (1993). Graft-versus-host disease after Brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK 506. Transplantation 55: 1–7PubMedCrossRefGoogle Scholar
  318. Renkonen R, Häyry P (1984). Bone marrow transplantation in the rat. I. Histologic correlation and quantification of cellular infiltrates in acute graft-versus-host disease. Am J Pathol 117: 462–470Google Scholar
  319. Schorlemmer HU, Seiler FR, Bartlett RR (1993). Prolongation of allogenetic transplanted skin grafts and induction of tolerance by leflunomide, a new immunosuppressive isoxyzol derivative. Transplant Proc 25: 763–767PubMedGoogle Scholar
  320. Shaffer D, Muanza T, Blakely M L, Simpson MA, Monaco AP (1993). Prevention of graft-versus-host-disease by RS-61443 in two different rodent models. Transplantation 55: 221–223PubMedCrossRefGoogle Scholar
  321. Thoenes GH, Sitter T, Langer KH, Bartlett RR, Schleyerbach R (1989). Leflunomide (HWA 486) inhibits experimental autoimmune tubulointerstitial nephritis in rats. Int J Immunopharmacol 11: 921–929PubMedCrossRefGoogle Scholar
  322. Wakely E, Oberholser JH, Cony RJ (1990) Elimination of acute GVHD and prolongation of rat pancreas allograft survival with DST, cyclosporine, and spleen transplantation. Transplantation 49: 241–245PubMedCrossRefGoogle Scholar
  323. Bartlett RR, Mattar T, Weithmann U, Anagnostopulos H, Popovic S, Schleyerbach R (1989) Leflunomide (HWA 486): a novel immunorestoring drug. In: Lewis AJ, Doherty NS, Ackerman NR (eds).Therapeutic approaches to inflammatory diseases. New York, Elsevier Science Publishing Co.. Inc., pp 215–228Google Scholar
  324. Bartlett RR, Popovic S, Raiss RX (1988) Development of autoimmunity in MRL/1pr mice and the effect of drugs on this murine disease. Scand. J. Rheumatol. Suppl. 75: 290–299Google Scholar
  325. Carlson RP, Baeder WL, Caccese RG, Warner LM, Sehgal SN (1992) Effects of orally administered rapamycin in animal models of arthritis and other autoimmune diseases. Ann NY Acad Sci 685: 86–113CrossRefGoogle Scholar
  326. Gunn HC, Hiestand PC (1988) Cyclosporine A and cyclosporine G enhance IgG rheumatoid factor production in MRL/Ipr Mice. Transplant Proc 20, Suppl 4: 238–242Google Scholar
  327. Schorlemmer HU, Dickneite G (1992) Preclinical studies with 15-deoxyspergualin in various animal models for autoimmune diseases. Ann NY Acad Sci 685: 155–174CrossRefGoogle Scholar
  328. Theofilopoulos AN, Dixon FJ (1981) Etiopathogenesis of murine SLE. Immunological Rev 55: 179–216CrossRefGoogle Scholar
  329. Damjanovic M, Vidic-Dankovic B, Kosec D, Isakovic K (1993). Thymus changes in experimentally induced myasthenia gravis. Autoimmunity: 15: 201–207PubMedCrossRefGoogle Scholar
  330. Drachman DB, Adams RN, McIntosh K, Pestronk A (1985) Treatment of experimental myasthenia gravis with cyclosporin A. Clin Immunol Immunopathol 34: 174–188PubMedCrossRefGoogle Scholar
  331. Itoyama Y, Kira J, Fuji N, Goto I, Yamamoto N (1989). Increases in helper inducer T cells and activated T cells in HTLV-1 associated myelopathy. Ann Neuro1: 26: 257–262CrossRefGoogle Scholar
  332. Lennon VA, Lambert EH, Leiby KR, Okarma TB, Talib S (1991). Recombinant human acetylcholine receptor a-subunit induces chronic experimental autoimmune myasthenia gravis. J Immunol, 146: 2245–2248PubMedGoogle Scholar
  333. McIntosh KR, Drachman DB (1986) Induction of suppressor cells specific for AChR in experimental autoimmune myasthenia gravis. Science 232: 401–403PubMedCrossRefGoogle Scholar
  334. McIntosh KR, Drachman DB (1987) Properties of suppressor cells induced to acetylcholine receptor using cyclosporin A. Ann NY Acad Sci 505: 628–638PubMedCrossRefGoogle Scholar
  335. Mrowka C, Thoenes GH, Langer KH, Bartlett RR (1994) Prevention of acute graft versus host disease ( GVHD) in rats by the immunomodulating drug leflunomide. Ann Hematology 68: 195–199Google Scholar
  336. Norcross NL, Griffith IJ, Lettieri JA (1980). Measurement of acetylcholine receptors and anti-receptor antibodies by ELISA. Muscle Nerve 3: 345–349PubMedCrossRefGoogle Scholar
  337. Oosterhuis H (1981). Observations of the natural history of myasthenia gravis and effect of thymectomy. Ann NY Acad Sci 377: 678–682PubMedCrossRefGoogle Scholar
  338. Ulrichs, K., Kaitschick, J., Bartlett, R., Müller-Ruchholtz, W. (1992) Suppression of natural xenophile antibodies with the novel immunosuppressive drug leflunomide. Transplant. Proc. 24: 718–719Google Scholar
  339. Williams JW, Xiao F, Foster P, Clardy C, McChesney L, Sankary H, Chong ASF (1994) Leflunomide in experimental transplantation. Control of rejection and alloantibody production, reversal of acute rejection, and interaction with cyclosporine. Transplantation 57: 1223–1231Google Scholar
  340. Aten J, Bosman CB, de Heer E, Hoedemaeker PJ, Weening JJ (1988) Cyclosporin A induces long-term unresponsiveness in mercuric chloride-induced autoimmune glomerulonephritis. Clin exp Immunol 73: 307–311PubMedGoogle Scholar
  341. Baran D, Vendeville B, Vial MC, Cosson C, Bascou C, Teychenne P, Druet P (1986) Effect of cyclosporin A on mercury-induced autoimmune glomerulonephritis in the Brown Norway rat. Clin Nephrol 25, Suppl 1: S175 — S180Google Scholar
  342. Cattran DC (1988) Effect of cyclosporin on active Heymann nephritis. Nephron 48: 142–148PubMedCrossRefGoogle Scholar
  343. Fujita M, Ilida H, Asaka M, Izumino K, Takata M, Sasayama S (1991) Effect of the immunosuppressive agent, cyclosporin, on experimental immune complex glomerulonephritis in rats. Nephron 57: 210–205CrossRefGoogle Scholar
  344. Giménez A, Leyva-Cobian F, Fiero C, Rio M, Bricio T, Mampaso F (1987) Effect of cyclosporin A on autoimmune tubulointerstitial nephritis in the brown Norway rat. Clin exp Immunol 69: 550–556PubMedGoogle Scholar
  345. Grönhagen-Riska C, von Willebrand E, Tikkanen T, Honkanen E, Miettinen A, Holthöfer H, Törnroth T (1990) The effect of cyclosporin A on the interstitial mononuclear cell infiltration and the induction of Heymann’s nephritis. Clin exp Immunol 79: 266–272PubMedCrossRefGoogle Scholar
  346. Heymann W, Hackel DB, Harwood S, Wilson SGF, Hunter JLP (1959) Production of nephrotic syndrome in rats by Freund’s adjuvants and rat kidney suspension. Proc Soc Exp Biol Med 100: 660–664PubMedGoogle Scholar
  347. Ito M, Yamada H, Okamoto K, Suzuki Y (1983) Crescentic type nephritis induced by anti-glomerular basement membrane ( GMB) serum in rats. Jap J Pharmacol 33: 1145–1154Google Scholar
  348. Kokui K, Yoshikawa N, Nakamura H, Itoh H (1992) Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis. J Pathol 166: 297–301PubMedCrossRefGoogle Scholar
  349. Lillevang ST, Rosenkvist J, Andersen CB, Larsen S, Kemp E, Kristensen T (1992) Single and combined effects of the vitamin D analogue KH1060 and cyclosporin A on mercuricchloride-induced autoimmune disease in the BN rat. Clin exp Immunol 88: 301–306PubMedCrossRefGoogle Scholar
  350. Ogawa T, Inazu M, Gotoh K, Hayashi S (1990) Effects of leflunomide on glomerulonephritis induced by antibasement membrane antibody in rats. Agents Actions 31: 321–328PubMedCrossRefGoogle Scholar
  351. Ogawa T, Inazu M, Gotoh K, Inoue T, Hayashi S (1991) Therapeutic effects of leflunomide, a new antirheumatic drug, on glomerulonephritis induced by the antibasement antibody in rats. Clin Immunol Immunopathol 61: 103–118PubMedCrossRefGoogle Scholar
  352. Reynolds J, Cashman SJ, Evans DJ, Pusey CD (1991) Cyclosporin A in the prevention and treatment of experimental autoimmune glomerulonephritis in the brown Norway rat. Clin Exp Immunol 85: 28–32PubMedCrossRefGoogle Scholar
  353. Schorlemmer HU, Dickneite G (1992) Preclinical studies with 15-deoxyspergualin in various animal models for autoimmune diseases. Ann NY Acad Sci 685: 155–174CrossRefGoogle Scholar
  354. Shibata S, Nagasawa T, Takuma T, Naruse T, Miyakawa Y, (1966) Isolation and properties of the soluble antigen specific for the production of nephrotoxic glomerulonephritis. I. Immunopathological demonstration of the complete antigenicity of the soluble antigen. Jpn J Exp Med 36: 127–143Google Scholar
  355. Shih W, Hines WH, Neilson EG (1988) Effects of cyclosporin A on the development of immune-mediated interstitial nephritis. Kidney Internat 33: 1113–1118CrossRefGoogle Scholar
  356. Thoenes GH, Sitter T, Langer KH, Bartlett RR, Schleyerbach R (1989) Leflunomide (HWA 486) inhibits experimental autoimmune tubulointerstitial nephritis in rats. Int J Immunopharmac 11: 921–929CrossRefGoogle Scholar
  357. Thoenes GH, Umscheid T, Sitter T, Langer KH (1987) Cyclosporin A inhibits autoimmune experimental tubulointerstitial nephritis. Immunol Lett 15: 301–306PubMedCrossRefGoogle Scholar
  358. Tipping PG, Holdsworth SR (1985) Effect of cyclosporin A on antibody-induced experimental glomerulonephritis. Nephron 40: 201–205PubMedCrossRefGoogle Scholar
  359. Tipping PG, Neale TJ, Holdsworth SR (1985) T lymphocyte participation in antibody-induced experimental glomerulonephritis. Kidney Internat 27: 530–537CrossRefGoogle Scholar
  360. Wilson CB (1981) Nephritogenic antibody mechanisms involving antigens within the glomerulus. Immunol Rev 55: 257–297PubMedCrossRefGoogle Scholar
  361. Wood A, Adu D, Birtwistle RJ, Brewer DB, Michael J (1988) Cyclosporin A and anti-glomerular basement membrane antibody glomerulonephritis in rats. Br J Path 69: 189–193Google Scholar
  362. Brockhuyse RM, Kuhlmann EC, van Vugt AHM, Winkens Hi (1987) Immunological and immunopathological aspects of opsin-induced uveoretinitis. Graefe’s Arch Clin Exp Ophthalmol 225: 45–49CrossRefGoogle Scholar
  363. Caspi RR, McAllister CG, Gery I, Nussenblatt RB (1988) Differential effects of cyclosporins A and G on functional activation of a T-helper-lymphocyte line mediating experimental autoimmune uveoretinitis. Cell Immunol 113: 350–360PubMedCrossRefGoogle Scholar
  364. Chan CC, Caspi R, Mochizuki M, Diamantstein T, Gery I, Nussenblatt RB (1987) Cyclosporine and dexamethasone inhibit T-lymphocyte MHC class II antigens and IL-2 receptor expression in experimental autoimmune uveitis. Immunol Invest 16: 319–331PubMedCrossRefGoogle Scholar
  365. Chan CC, Palestine AG, Nussenblatt RB (1984) Cyclosporineinduced alterations of humoral response in experimental autoimmune uveitis. Invest Ophthalmol Vis Sci 25: 867–870PubMedGoogle Scholar
  366. de Kozak Y, Sakai J, Thillaye B, Faure JP (1982) S antigen-induced experimental autoimmune uveo-retinitis in rats. Curr Eye Res 1: 327–337CrossRefGoogle Scholar
  367. Fujino Y, Okumura A, Nussenblatt RB, Gery I, Mochizuki M (1988) Cyclosporine-induced specific unresponsiveness to retinal soluble antigen in experimental autoimmune uveoretinitis. Clin Immunol Immunopathol 46: 234–248PubMedCrossRefGoogle Scholar
  368. Jamieson L, Meckoll-Brinck D, Keller N (1989) Characterized and predictable rabbit uveitis model for antiinflammatory drug screening. J Pharmacol Meth 21: 329–338CrossRefGoogle Scholar
  369. Kaswan RL, Kaplan RI (1988) Comparison of the efficacy of unilateral, bilateral, and oral cyclosporine in experimental immunogenic uveitis in rabbits. Transplant Proc 20, Suppl 4: 149–157Google Scholar
  370. Liversidge J, Thompson AW, Sewell HF, Forrester JV (1987) EAU in the guinea pig: inhibition of cell-mediated immunity and Ia antigen expression by cyclosporin A. Clin exp Immunol 69: 591–600PubMedGoogle Scholar
  371. Liversidge J, Thomson AW, Sewell HF, Forrester JV (1988) Cyclosporine A, experimental autoimmune uveitis, and major histocompatibility class II antigen expression of cultured retinal pigment epithelial cells. Transplant Proc 20, Suppl 4: 163–169Google Scholar
  372. Mahlberg K, Uusitalo H, Uusitalo R, Palkama A, Tallberg T (1987) Suppression of experimental autoimmune uveitis in guinea pigs by ethylenediamine tetra-acetic acid, corticosteroids and cyclosporin. J Ocul Pharmacol 3: 199–210PubMedCrossRefGoogle Scholar
  373. Mochizuki M, Nussenblatt RB, Kuwabara T, Gery I (1985) Effects of cyclosporine and other immunosuppressive drugs on experimental autoimmmune uveoretinitis in rats. Invest Ophthalmol Vis Sci 26: 226–232PubMedGoogle Scholar
  374. Nordmann JP, de Kozak Y, Le Hoang P, Faure JP (1986) Cyclosporine therapy of guinea-pig autoimmune uveitis induced with autologous retina. J Ocul Pharmacol 2: 325–333PubMedCrossRefGoogle Scholar
  375. Nussenblatt RB, Rodrigues MM, Wacker WB, Cevario SJ, Salinas-Carmona MC (1981) Inhibition of experimental autoimmune uveitis in Lewis rats. J Clin Invest 67: 1228–1231PubMedCrossRefGoogle Scholar
  376. Smith-Lang L, Glaser RL, Miller ST, Weimer LK, Robertson SM, Aoki KR, Yanni JM (1992) Efficacy of novel immunomodulators leflunomide and rapamycin in autoimmune uveitis. FASEB J 6:A1048, Part 1Google Scholar
  377. Wacker WB, Lipton MM (1965) Experimental allergic uveitis: homologous retina as uveitigenic antigen. Nature 206: 253–254PubMedCrossRefGoogle Scholar
  378. Wacker WB, Lipton MM, Ongchua FE (1964) Antibody production in the guinea pig to homologous uvea. Proc Soc Exp Biol Med 117: 150–154PubMedGoogle Scholar
  379. Adams DH, Tiney NL, Collins JJ, Karnovsky MJ (1992) Experimental graft arteriosclerosis. Transplantation 53: 11 15 1119Google Scholar
  380. Almond PS, Moss A, Nakhleh R, Melin M, Chen S, Salazar A, Shirabe K, Matas A (1992) Rapamycin in a renal transplant model. Ann NY Acad Sci 685: 121–122CrossRefGoogle Scholar
  381. Bartlett RR, Dimitrijevic M, Mattar T, Zielinski T, Germann T, Rüde E, Thoenes G H, Küchle CCA, Schorlemmer HU, Bremer E, Finnegan A, Schleyerbach R (1991). Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of auto-immune disorders and reactions leading to transplantation rejection. Agents and Actions 32: 11–21CrossRefGoogle Scholar
  382. Coupland SE, Klebe S, Karow AC, Krause L, Kruse H, Bartlett RR, Hoffmann F (1994) Leflunomide therapy following penetrating keratoplasty in the rat. Graefe’s Arch Clin Exp Ophthalmol 232: 622–627PubMedCrossRefGoogle Scholar
  383. Cramer DV, Chapman FA, Wu GD, Harnaha JB, Qian S, Makowka L (1990) Cardiac transplantation in the rat. Transplantation 50: 554–558PubMedCrossRefGoogle Scholar
  384. Davreux CJ, Chu NH, Waddell TK, Mayer E, Patterson GA (1993) Improved tracheal allograft viability in immunosuppressed rats. Ann Thorac Surg 55: 131–134PubMedCrossRefGoogle Scholar
  385. de Masi R. Algaisi M, Araneda D, Nifong W, Thomas J, Gross U, Swanson M, Thomas F (1990) Reevaluation of total-lymphoid irradiation and cyclosporine therapy in the Syrian hamster-to-Lewis rat cardiac xenograft model. Transplantation 49: 639–641Google Scholar
  386. Engelbrecht G, Kahn D, Duminy F, Hickman R (1992) New rapid technique for renal transplantation in the rat. Microsurg 13: 340–344CrossRefGoogle Scholar
  387. Fujino Y, Kawamura T, Hullett DA, Sollinger HW (1994) Evaluation of cyclosporine, mycophenolate mofetil, and brequinar sodium combination therapy on hamster-to-rat cardiac xenotransplantation. Transplantation 57: 41–46PubMedCrossRefGoogle Scholar
  388. Hancock WW, diStefano R, Braun P, Schweizer RT, Tilney NL, Kupiec-Weglinski JW (1990) Cyclosporin and antiinterleukin 2 receptor monoclonal antibody therapy suppress accelerated rejection of rat cardiac allografts through different effector mechanisms. Transplantation 49: 416–421PubMedCrossRefGoogle Scholar
  389. Kahn DR, Forrest DE, Otto DA (1991) Prolonged survival of rat cardiac allografts by donor pretreatment with methotrexate. Transplantation 51: 697–700PubMedCrossRefGoogle Scholar
  390. Katayama Y, Yada I, Namikawa S, Kusagawa M (1991) Immunosuppressive effects of FK 506 in rat lung transplantation. Transplant Proc 23: 3300–3301PubMedGoogle Scholar
  391. Kellnar S, Herkomer C, Bae S, Schumacher U (1990) Allogenic transplantation of fetal rat intestine: anastomosis to the normal bowel of the host. J Pediatr Surg 25: 415–417PubMedCrossRefGoogle Scholar
  392. Kirsch AJ, Kirsch SS, Kimura K, LaRosa CA, Jaffe BM (1991) The adaptive ability of transplanted rat small intestine. Surgery 109: 779–787PubMedGoogle Scholar
  393. Kobayashi J, Mavroudis C, Crawford SE, Zales VR, Backer CL (1993) A new rat infection-heart transplant model: effect of infection on graft survival studies. J Heart Lung Transplant 12: 659–664PubMedGoogle Scholar
  394. Küchle CCA, Thoenes GH, Langer KH, Schorlemmer HU, Bartlett RR, Schleyerbach R (1991). Prevention of kidney and skin graft rejection in rats by leflunomide, a new immunomodulating agent. Transplant Proc 23: 1083–1086PubMedGoogle Scholar
  395. Kuroki H, Ishida O, Daisaku H, Fukuhara K, Hatano E, Murakami T, Ikuta Y, Matsumoto AK, Akiyama M (1991) Morphological and immunological analysis of rats with long-term-surviving limb allografts induced by a short course of FK 506 or cyclosporine. Transplant Proc 23: 516–520PubMedGoogle Scholar
  396. Langrehr JM, Hoffman RA, Banner B, Stangl MJ, Monyhan H, Le KKW, Schraut WH (1991) Induction of graft-versushost disease and rejection by sensitized small bowel allografts. Transplantation 52: 399–405PubMedCrossRefGoogle Scholar
  397. Lee WP, Pan YC, Kesmarky S, Randolph MA, Fiala TS, Amarante MTJ, Weiland AJ, Yaremchuk MJ (1995) Experimental orthotopic transplantation of vascularized skeletal allografts: functional assessment and long-term survival. Plast Reconstr Surg 95: 336–353PubMedCrossRefGoogle Scholar
  398. McManus RP, O’Hair DP, Komorowski R, Scott JP (1993) Immunosuppressant combinations in primate cardiac xenografts. Ann NY Acad Sci 969: 281–284Google Scholar
  399. Mennander A, Tiisala S, Paavonen T, Halttunen J, Häyry P (1991). Chronic rejection of rat aortic allograft. II. Administration of cyclosporin induces accelerated allograft arteriosclerosis. Transplant Int 4: 173–179Google Scholar
  400. Muramatsu K, Doi K, Kawai S (1994) The outcome of neurovascularized allogeneic muscle transplantation under immunosuppression with cyclosporine. J Reconstr Microsurg 10: 77–81PubMedCrossRefGoogle Scholar
  401. Murase N, Demetris A J, Woo J, Tanabe M, Furuya T, Todo S, Strazl T E (1993). Graft-versus-host disease after Brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK 506. Transplantation 55: 1–7PubMedCrossRefGoogle Scholar
  402. Nemoto K, Sugawara Y, Mae T, Hayashi M, Abe F, Fujii A, Takeuchi T (1992) Therapeutic activity of deoxyspergualin in comparison with cyclosporin A, and its combined use with cyclosporin A and prednisolone in highly allogeneic skin transplantation in the rat. Agents Actions 36: 306–311PubMedGoogle Scholar
  403. Schorlemmer HU, Seiler FR, Bartlett RR (1993). Prolongation of allogenetic transplanted skin grafts and induction of tolerance by leflunomide, a new immunosuppressive isoxyzol derivative. Transplant Proc 25: 763–767PubMedGoogle Scholar
  404. Schuurman HJ, Joergensen J, Kuipers H, Meerloo T, Lardelli P, Hiestand P, White DH, Schreier MH (1994) Vascular transplantation of Syrian hamster heart into Lewis rat: effect of brequinar, cyclosporine, cobra venom factor, and splenectomy. Transplant Proc 26: 1217–1219PubMedGoogle Scholar
  405. Shaffer D, Muanza T, Blakely M L, Simpson M A, Monaco A P (1993). Prevention of graft-versus-host-disease by RS-61443 in two different rodent models. Transplantation 55: 221–223PubMedCrossRefGoogle Scholar
  406. Steinbrüchel DA, Madsen HH, Nielsen B, Kemp E, Larsen S, Koch C (1991) The effect of combined treatment with total lymphoid irradiation, cyclosporin A, and anti-CD4 monoclonal antibodies in a hamster-to-rat heart transplantation model. Transplant Proc 23: 579–580PubMedGoogle Scholar
  407. Svensson G, Holmberg SB, Friman S (1995) Influence of liver transplantation and cyclosporin on bile secretion — an experimental study in the rat. Transpl Int 8: 27–34PubMedGoogle Scholar
  408. Ulrichs, K., Kaitschick, J., Bartlett, R., Muller-Ruchholtz, W. (1992) Suppression of natural xenophile antibodies with the novel immunomodulating drug leflunomide. Transplant. Proc. 24: 718–719Google Scholar
  409. van den Bogaerde J, Aspinall R, Wang MW, Cary N, Lim S, Wright L, White D (1991) Induction of long-term survival of hamster heart xenografts in rats. Transplantation 52: 15–20PubMedCrossRefGoogle Scholar
  410. Walpoth BH, Tschopp A, Lazeyras F, Galdikas J, Tschudi J, Altermatt H, Schaffner T, Aue WP, Althaus U (1993) Magnetic resonance spectroscopy for assessing myocardial rejection in the transplanted rat heart. J Heart Lung Transplant 12: 271–282PubMedGoogle Scholar
  411. Williams JW, Xiao F, Foster P, Chong A, Sharma S, Bartlett RR, Sankary HN (1993) Immunosuppressive effects of leflunomide in a cardiac allograft model. Transplant Proc 25: 745–746PubMedGoogle Scholar
  412. Williams JW, Xiao F, Foster P, Clardy C, McChesney L, Sankary H, Chong ASF (1994) Leflunomide in experimental transplantation. Control of rejection and alloantibody production, reversal of acute rejection, and interaction with cyclosporine. Transplantation 57: 1223–1231Google Scholar
  413. Woo J, Valdivia LA, Pan F, Celli S, Fing JJ, Thomson AW (1993) Cytidine potentiates the inhibitory effect of brequinar sodium on xeno-MLR, antibody production, and concordant hamster to rat cardiac xenograft survival. Ann NY Acad Sci 969: 227–234Google Scholar
  414. Xia W, Kirkman RL (1990), Immune function in transplanted small intestine. Transplantation 49: 277–280PubMedCrossRefGoogle Scholar
  415. Xiao F, Chong ASF, Bartlett RR, Williams JW (1994) Leflunomide: a promising immunosuppressant in transplantation. In: Thomson AW, Starzl ThE (eds) Immunosuppressive Drugs. Edward Arnold, London, Boston, Melbourne, pp 203–212Google Scholar
  416. Yu LT, England J, Sumner A, Larossa D, Hickey WF (1990) Electrophysiologic evaluation of peripheral nerve regeneration through allografts immunosuppressed with cyclosporin. J Reconstr Microsurg 6: 317–323PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  1. 1.Johann Wolfgang Goethe Universität FrankfurtFrankfurt am MainGermany
  2. 2.Philipps Universität MarburgMarburgGermany
  3. 3.Department of Pharmacology Jefferson Medical CollegeThomas Jefferson UniversityPhiladelphiaUSA

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