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The Role of Cytokines in the Mechanism of Adverse Drug Reactions

  • Mary Jane MassonEmail author
  • Lindsay A. Collins
  • Lance R. Pohl
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 196)

Abstract

Cytokines are thought to play a role in acute and/or immune-mediated adverse drug reactions (ADRs) due to their ability to regulate the innate and adaptive immune systems. This role is highly complex owing to the pluripotent nature of cytokines, which enables the same cytokine to play multiple roles depending on target organ(s) involved. As a result, the discussion of cytokine involvement in ADRs is organized according to target organ(s); specifically, ADRs targeting skin and liver, as well as ADRs targeting multiple organs, such as drug-induced autoimmunity and infusion-related reactions. In addition to discussing the mechanism(s) by which cytokines contribute to the initiation, propagation, and resolution of ADRs, we also discuss the usefulness and limitations of current methodologies available to conduct such mechanistic studies. While animal models appear to hold the most promise for uncovering additional mechanisms, this field is plagued by a lack of good animal models and, as a result, the mechanism of cytokine involvement in ADRs is often studied using less informative in vitro studies. The recent formation of the Drug-Induced Liver Injury Network, whose goal is collect thousands of samples from drug-induced liver injury patients, has enormous potential to advance knowledge in this field, by enabling large-scale cytokine polymorphism studies. In conclusion, we discuss how further advances in this field could be of significant benefit to patients in terms of preventing, predicting, and treating ADRs.

Keywords

Cytokines Immune-mediated adverse drug reactions Skin Drug-induced autoimmunity Drug-induced liver injury 

References

  1. Aarvak T, Chabaud M, Miossec P, Natvig JB (1999) IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells. J Immunol 162:1246-1251PubMedGoogle Scholar
  2. Ackerman Z, Levy M (1987) Hypersensitivity reactions to drugs in acquired immunodeficiency syndrome. Postgrad Med J 63:55-56PubMedGoogle Scholar
  3. Aithal GP, Ramsay L, Daly AK, Sonchit N, Leathart JB, Alexander G, Kenna JG, Caldwell J, Day CP (2004) Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity. Hepatology 39:1430-1440PubMedGoogle Scholar
  4. Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y (2005) Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129:969-984PubMedGoogle Scholar
  5. Antunez C, Martin E, Cornejo-Garcia JA, Blanca-Lopez N, RP R, Mayorga C, Torres MJ, Blanca M (2006) Immediate hypersensitivity reactions to penicillins and other betalactams. Curr Pharm Des 12:3327-3333PubMedGoogle Scholar
  6. Baugh JA, Bucala R (2002) Macrophage migration inhibitory factor. Crit Care Med 30:S27-S35Google Scholar
  7. Bautista AP (1997) Chronic alcohol intoxication induces hepatic injury through enhanced macrophage inflammatory protein-2 production and intercellular adhesion molecule-1 expression in the liver. Hepatology 25:335-342PubMedGoogle Scholar
  8. Benghiat FS, Charbonnier LM, Vokaer B, De Wilde V, Le Moine A (2009) Interleukin 17-producing T helper cells in alloimmunity. Transplant Rev (Orlando) 23:11-18Google Scholar
  9. Bernal W, Donaldson P, Underhill J, Wendon J, Williams R (1998) Tumor necrosis factor genomic polymorphism and outcome of acetaminophen (paracetamol)-induced acute liver failure. J Hepatol 29:53-59PubMedGoogle Scholar
  10. Beyer HS, Stanley M (1990) Tumor necrosis factor-alpha increases hepatic DNA and RNA and hepatocyte mitosis. Biochem Int 22:405-410PubMedGoogle Scholar
  11. Bienvenu J, Chvetzoff R, Salles G, Balter C, Tilly H, Herbrecht R, Morel P, Lederlin P, Solal-Celigny P, Audhuy B, Christian B, Gabarre J, Casasnovas O, Marit G, Sebban C, Coiffier B (2001) Tumor necrosis factor alpha release is a major biological event associated with rituximab treatment. Hematol J 2:378-384PubMedGoogle Scholar
  12. Bissell DM, Gores GJ, Laskin DL, Hoofnagle JH (2001) Drug-induced liver injury: mechanisms and test systems. Hepatology 33:1009-1013PubMedGoogle Scholar
  13. Blazka ME, Wilmer JL, Holladay SD, Wilson RE, Luster MI (1995) Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 133:43-52PubMedGoogle Scholar
  14. Blenman KR, Duan B, Xu Z, Wan S, Atkinson MA, Flotte TR, Croker BP, Morel L (2006) IL-10 regulation of lupus in the NZM2410 murine model. Lab Invest 86:1136-1148PubMedGoogle Scholar
  15. Boess F, Bopst M, Althaus R, Polsky S, Cohen SD, Eugster HP, Boelsterli UA (1998) Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-alpha gene knockout mice. Hepatology 27:1021-1029PubMedGoogle Scholar
  16. Bogdan C, Vodovotz Y, Nathan C (1991) Macrophage deactivation by interleukin 10. J Exp Med 174:1549-1555PubMedGoogle Scholar
  17. Bourdi M, Amouzadeh HR, Rushmore TH, Martin JL, Pohl LR (2001) Halothane-induced liver injury in outbred guinea pigs: role of trifluoroacetylated protein adducts in animal susceptibility. Chem Res Toxicol 14:362-370PubMedGoogle Scholar
  18. Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, Shah AG, Pohl LR (2002a) Protection against acetaminophen-induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase. Hepatology 35:289-298PubMedGoogle Scholar
  19. Bourdi M, Reilly TP, Elkahloun AG, George JW, Pohl LR (2002b) Macrophage migration inhibitory factor in drug-induced liver injury: a role in susceptibility and stress responsiveness. Biochem Biophys Res Commun 294:225-230PubMedGoogle Scholar
  20. Bourdi M, Eiras DP, Holt MP, Webster MR, Reilly TP, Welch KD, Pohl LR (2007) Role of IL-6 in an IL-10 and IL-4 double knockout mouse model uniquely susceptible to acetaminophen-induced liver injury. Chem Res Toxicol 20:208-216PubMedGoogle Scholar
  21. Britschgi M, Steiner UC, Schmid S, Depta JP, Senti G, Bircher A, Burkhart C, Yawalkar N, Pichler WJ (2001) T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest 107:1433-1441PubMedGoogle Scholar
  22. Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A (1999) Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163:4647-4650PubMedGoogle Scholar
  23. Carr DF, Alfirevic A, Tugwood JD, Barratt BJ, Sherwood J, Smith J, Pirmohamed M, Park BK (2007) Molecular and genetic association of interleukin-6 in tacrine-induced hepatotoxicity. Pharmacogenet Genom 17:961-972Google Scholar
  24. Cattell V, Lianos E, Largen P, Cook T (1993) Glomerular NO synthase activity in mesangial cell immune injury. Exp Nephrol 1:36-40PubMedGoogle Scholar
  25. Chaouchi N, Wallon C, Taieb J, Auffredou MT, Tertian G, Lemoine FM, Delfraissy JF, Vazquez A (1994) Interferon-alpha-mediated prevention of in vitro apoptosis of chronic lymphocytic leukemia B cells: role of bcl-2 and c-myc. Clin Immunol Immunopathol 73:197-204PubMedGoogle Scholar
  26. Chen M, Gandolfi J (1997) Characterization of the humoral immune response and hepatotoxicity after multiple halothane exposures in guinea pigs. Drug Metab Rev 29:103-122PubMedGoogle Scholar
  27. Chiaramonte MG, Cheever AW, Malley JD, Donaldson DD, Wynn TA (2001) Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis. Hepatology 34:273-282PubMedGoogle Scholar
  28. Chiu H, Brittingham JA, Laskin DL (2002) Differential induction of heme oxygenase-1 in macrophages and hepatocytes during acetaminophen-induced hepatotoxicity in the rat: effects of hemin and biliverdin. Toxicol Appl Pharmacol 181:106-115PubMedGoogle Scholar
  29. Choquet-Kastylevsky G, Intrator L, Chenal C, Bocquet H, Revuz J, Roujeau JC (1998) Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome. Br J Dermatol 139:1026-1032PubMedGoogle Scholar
  30. Clynes RA, Towers TL, Presta LG, Ravetch JV (2000) Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6:443-446PubMedGoogle Scholar
  31. Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V, Taub R (1996) Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274:1379-1383PubMedGoogle Scholar
  32. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744-748PubMedGoogle Scholar
  33. Cumberbatch M, Dearman RJ, Antonopoulos C, Groves RW, Kimber I (2001) Interleukin (IL)-18 induces Langerhans cell migration by a tumour necrosis factor-alpha- and IL-1beta-dependent mechanism. Immunology 102:323-330PubMedGoogle Scholar
  34. Dambach DM, Watson LM, Gray KR, Durham SK, Laskin DL (2002) Role of CCR2 in macrophage migration into the liver during acetaminophen-induced hepatotoxicity in the mouse. Hepatology 35:1093-1103PubMedGoogle Scholar
  35. Delespesse G, Suter U, Mossalayi D, Bettler B, Sarfati M, Hofstetter H, Kilcherr E, Debre P, Dalloul A (1991) Expression, structure, and function of the CD23 antigen. Adv Immunol 49:149-191PubMedGoogle Scholar
  36. Devalaraja MN, McClain CJ, Barve S, Vaddi K, Hill DB (1999) Increased monocyte MCP-1 production in acute alcoholic hepatitis. Cytokine 11:875-881PubMedGoogle Scholar
  37. Diehl AM (2000) Cytokine regulation of liver injury and repair. Immunol Rev 174:160-171PubMedGoogle Scholar
  38. Diehl AM, Rai RM (1996) Liver regeneration 3: Regulation of signal transduction during liver regeneration. FASEB J 10:215-227PubMedGoogle Scholar
  39. DiPietro LA (1995) Wound healing: the role of the macrophage and other immune cells. Shock 4:233-240PubMedGoogle Scholar
  40. Donker AJ, Venuto RC, Vladutiu AO, Brentjens JR, Andres GA (1984) Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Brown Norway rats treated with D-penicillamine develop autoantibodies, circulating immune complexes, and disseminated intravascular coagulation. Clin Immunol Immunopathol 30:142-155PubMedGoogle Scholar
  41. Enzenauer RJ, West SG, Rubin RL (1990) D-penicillamine-induced lupus erythematosus. Arthritis Rheum 33:1582-1585PubMedGoogle Scholar
  42. Finck BK, Chan B, Wofsy D (1994) Interleukin 6 promotes murine lupus in NZB/NZW F1 mice. J Clin Invest 94:585-591PubMedGoogle Scholar
  43. Fong TA, Mosmann TR (1989) The role of IFN-gamma in delayed-type hypersensitivity mediated by Th1 clones. J Immunol 143:2887-2893PubMedGoogle Scholar
  44. Fournie GJ, Cautain B, Xystrakis E, Damoiseaux J, Mas M, Lagrange D, Bernard I, Subra JF, Pelletier L, Druet P, Saoudi A (2001) Cellular and genetic factors involved in the difference between Brown Norway and Lewis rats to develop respectively type-2 and type-1 immune-mediated diseases. Immunol Rev 184:145-160PubMedGoogle Scholar
  45. Friedmann PS, Strickland I, Pirmohamed M, Park BK (1994) Investigation of mechanisms in toxic epidermal necrolysis induced by carbamazepine. Arch Dermatol 130:598-604PubMedGoogle Scholar
  46. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52:65-70PubMedGoogle Scholar
  47. Ganey PE, Luyendyk JP, Maddox JF, Roth RA (2004) Adverse hepatic drug reactions: inflammatory episodes as consequence and contributor. Chem Biol Interact 150:35-51PubMedGoogle Scholar
  48. Gao B (2005) Cytokines, STATs and liver disease. Cell Mol Immunol 2:92-100PubMedGoogle Scholar
  49. Gao PS, Mao XQ, Jouanguy E, Pallier A, Doffinger R, Tanaka Y, Nakashima H, Otsuka T, Roberts MH, Enomoto T, Dake Y, Kawai M, Sasaki S, Shaldon SR, Coull P, Adra CN, Niho Y, Casanova JL, Shirakawa T, Hopkin JM (1999) Nonpathogenic common variants of IFNGR1 and IFNGR2 in association with total serum IgE levels. Biochem Biophys Res Commun 263:425-429PubMedGoogle Scholar
  50. Gardner CR, Laskin JD, Dambach DM, Chiu H, Durham SK, Zhou P, Bruno M, Gerecke DR, Gordon MK, Laskin DL (2003) Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1. Potential role of inflammatory mediators. Toxicol Appl Pharmacol 192:119-130PubMedGoogle Scholar
  51. Geddes R (2007) Minocycline-induced lupus in adolescents: clinical implications for physical therapists. J Orthop Sports Phys Ther 37:65-71PubMedGoogle Scholar
  52. Grove J, Daly AK, Bassendine MF, Gilvarry E, Day CP (2000) Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease. Gut 46:540-545PubMedGoogle Scholar
  53. Groves RW, Allen MH, Ross EL, Barker JN, MacDonald DM (1995) Tumour necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression. Br J Dermatol 132:345-352PubMedGoogle Scholar
  54. Guglielmi L, Fontaine C, Gougat C, Avinens O, Eliaou JF, Guglielmi P, Demoly P (2006a) IL-10 promoter and IL4-Ralpha gene SNPs are associated with immediate beta-lactam allergy in atopic women. Allergy 61:921-927PubMedGoogle Scholar
  55. Guglielmi L, Guglielmi P, Demoly P (2006b) Drug hypersensitivity: epidemiology and risk factors. Curr Pharm Des 12:3309-3312PubMedGoogle Scholar
  56. Gunawan BK, Kaplowitz N (2007) Mechanisms of drug-induced liver disease. Clin Liver Dis 11:459-475, vGoogle Scholar
  57. Gutierrez A, Rodriguez J, Martinez J, Amezaga R, Ramos R, Galmes B, Bea MD, Ferrer J, Pons J, Sampol A, Morey M, Duran MA, Raurich J, Besalduch J (2006) Pathogenic study of anti-CD20 infusion-related severe refractory shock in diffuse large B-cell lymphoma. Leuk Lymphoma 47:111-115PubMedGoogle Scholar
  58. Happ MP, Wettstein P, Dietzschold B, Heber-Katz E (1988) Genetic control of the development of experimental allergic encephalomyelitis in rats. Separation of MHC and non-MHC gene effects. J Immunol 141:1489-1494PubMedGoogle Scholar
  59. Herber D, Brown TP, Liang S, Young DA, Collins M, Dunussi-Joannopoulos K (2007) IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol 178:3822-3830PubMedGoogle Scholar
  60. Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA (1997) The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med 337:1720-1725PubMedGoogle Scholar
  61. Hill DB, Marsano L, Cohen D, Allen J, Shedlofsky S, McClain CJ (1992) Increased plasma interleukin-6 concentrations in alcoholic hepatitis. J Lab Clin Med 119:547-552PubMedGoogle Scholar
  62. Hogaboam CM, Simpson KJ, Chensue SW, Steinhauser ML, Lukacs NW, Gauldie J, Strieter RM, Kunkel SL (1999) Macrophage inflammatory protein-2 gene therapy attenuates adenovirus- and acetaminophen-mediated hepatic injury. Gene Ther 6:573-584PubMedGoogle Scholar
  63. Hogaboam CM, Bone-Larson CL, Steinhauser ML, Matsukawa A, Gosling J, Boring L, Charo IF, Simpson KJ, Lukacs NW, Kunkel SL (2000) Exaggerated hepatic injury due to acetaminophen challenge in mice lacking C-C chemokine receptor 2. Am J Pathol 156:1245-1252PubMedGoogle Scholar
  64. Huang YH, Shi MN, Zheng WD, Zhang LJ, Chen ZX, Wang XZ (2006) Therapeutic effect of interleukin-10 on CCl4-induced hepatic fibrosis in rats. World J Gastroenterol 12:1386-1391PubMedGoogle Scholar
  65. Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M (1994) Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 179:305-310PubMedGoogle Scholar
  66. Ishida Y, Kondo T, Ohshima T, Fujiwara H, Iwakura Y, Mukaida N (2002) A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen-induced acute liver injury. FASEB J 16:1227-1236PubMedGoogle Scholar
  67. Ishida Y, Kondo T, Tsuneyama K, Lu P, Takayasu T, Mukaida N (2004) The pathogenic roles of tumor necrosis factor receptor p55 in acetaminophen-induced liver injury in mice. J Leukoc Biol 75:59-67PubMedGoogle Scholar
  68. Jacob CO, Hwang F, Lewis GD, Stall AM (1991) Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: implications for genetic predisposition and immune regulation. Cytokine 3:551-561PubMedGoogle Scholar
  69. James LP, Lamps LW, McCullough S, Hinson JA (2003) Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse. Biochem Biophys Res Commun 309:857-863PubMedGoogle Scholar
  70. James LP, Kurten RC, Lamps LW, McCullough S, Hinson JA (2005a) Tumour necrosis factor receptor 1 and hepatocyte regeneration in acetaminophen toxicity: a kinetic study of proliferating cell nuclear antigen and cytokine expression. Basic Clin Pharmacol Toxicol 97:8-14PubMedGoogle Scholar
  71. James LP, Simpson PM, Farrar HC, Kearns GL, Wasserman GS, Blumer JL, Reed MD, Sullivan JE, Hinson JA (2005b) Cytokines and toxicity in acetaminophen overdose. J Clin Pharmacol 45:1165-1171PubMedGoogle Scholar
  72. Jarrett SJ, Cunnane G, Conaghan PG, Bingham SJ, Buch MH, Quinn MA, Emery P (2003) Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series. J Rheumatol 30:2287-2291PubMedGoogle Scholar
  73. Jaruga B, Hong F, Sun R, Radaeva S, Gao B (2003) Crucial role of IL-4/STAT6 in T cell-mediated hepatitis: up-regulating eotaxins and IL-5 and recruiting leukocytes. J Immunol 171:3233-3244PubMedGoogle Scholar
  74. Ju C, Reilly TP, Bourdi M, Radonovich MF, Brady JN, George JW, Pohl LR (2002) Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice. Chem Res Toxicol 15:1504-1513PubMedGoogle Scholar
  75. Kaplowitz N, Tsukamoto H (1996) Oxidative stress and liver disease. Prog Liver Dis 14:131-159PubMedGoogle Scholar
  76. Kato A, Yoshidome H, Edwards MJ, Lentsch AB (2000) Reduced hepatic ischemia/reperfusion injury by IL-4: potential anti-inflammatory role of STAT6. Inflamm Res 49:275-279PubMedGoogle Scholar
  77. Kato A, Okaya T, Lentsch AB (2003) Endogenous IL-13 protects hepatocytes and vascular endothelial cells during ischemia/reperfusion injury. Hepatology 37:304-312PubMedGoogle Scholar
  78. Kellokumpu-Lehtinen P, Iisalo E, Nordman E (1989) Hepatotoxicity of paracetamol in combination with interferon and vinblastine. Lancet 1:1143PubMedGoogle Scholar
  79. Khan FD, Roychowdhury S, Gaspari AA, Svensson CK (2006) Immune response to xenobiotics in the skin: from contact sensitivity to drug allergy. Expert Opin Drug Metab Toxicol 2:261-272PubMedGoogle Scholar
  80. Kleinschmidt WJ, Schultz RM (1982) Similarities of murine gamma interferon and the lymphokine that renders macrophages cytotoxic. J Interferon Res 2:291-299PubMedGoogle Scholar
  81. Knolle PA, Uhrig A, Hegenbarth S, Loser E, Schmitt E, Gerken G, Lohse AW (1998) IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules. Clin Exp Immunol 114:427-433PubMedGoogle Scholar
  82. Kobayashi S, Nishihira J, Watanabe S, Todo S (1999) Prevention of lethal acute hepatic failure by antimacrophage migration inhibitory factor antibody in mice treated with bacille Calmette-Guerin and lipopolysaccharide. Hepatology 29:1752-1759PubMedGoogle Scholar
  83. Kollias G, Kontoyiannis D (2002) Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments. Cytokine Growth Factor Rev 13:315-321PubMedGoogle Scholar
  84. Kovalovich K, Li W, DeAngelis R, Greenbaum LE, Ciliberto G, Taub R (2001) Interleukin-6 protects against Fas-mediated death by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl-xL. J Biol Chem 276:26605-26613PubMedGoogle Scholar
  85. Kretz-Rommel A, Duncan SR, Rubin RL (1997) Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus. J Clin Invest 99:1888-1896PubMedGoogle Scholar
  86. Kroemer G, Hirsch F, Gonzalez-Garcia A, Martinez C (1996) Differential involvement of Th1 and Th2 cytokines in autoimmune diseases. Autoimmunity 24:25-33PubMedGoogle Scholar
  87. Kuby J (1997) Immunology, 3rd edn. W. H. Freeman & Company, New YorkGoogle Scholar
  88. La Flamme AC, Patton EA, Bauman B, Pearce EJ (2001) IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis. J Immunol 166:1903-1911PubMedGoogle Scholar
  89. Lacour S, Gautier JC, Pallardy M, Roberts R (2005) Cytokines as potential biomarkers of liver toxicity. Cancer Biomark 1:29-39PubMedGoogle Scholar
  90. Lazarus M, Hajeer AH, Turner D, Sinnott P, Worthington J, Ollier WE, Hutchinson IV (1997) Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus. J Rheumatol 24:2314-2317PubMedGoogle Scholar
  91. Le Moine O, Louis H, Sermon F, Goldman M, Deviere J (1999) Interleukin-10 and liver diseases. Acta Gastroenterol Belg 62:1-8PubMedGoogle Scholar
  92. Leeder JS, Kearns GL (1997) Pharmacogenetics in pediatrics. Implications for practice. Pediatr Clin North Am 44:55-77PubMedGoogle Scholar
  93. Leifeld L, Dumoulin FL, Purr I, Janberg K, Trautwein C, Wolff M, Manns MP, Sauerbruch T, Spengler U (2003) Early up-regulation of chemokine expression in fulminant hepatic failure. J Pathol 199:335-344PubMedGoogle Scholar
  94. Lentsch AB, Yoshidome H, Cheadle WG, Miller FN, Edwards MJ (1998) Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and Kupffer cells. Hepatology 27:507-512PubMedGoogle Scholar
  95. Liew FY, Li Y, Millott S (1990) Tumour necrosis factor (TNF-alpha) in leishmaniasis. II. TNF-alpha-induced macrophage leishmanicidal activity is mediated by nitric oxide from L-arginine. Immunology 71:556-559PubMedGoogle Scholar
  96. Lim S, Crawley E, Woo P, Barnes PJ (1998) Haplotype associated with low interleukin-10 production in patients with severe asthma. Lancet 352:113PubMedGoogle Scholar
  97. Liu ZX, Kaplowitz N (2002) Immune-mediated drug-induced liver disease. Clin Liver Dis 6:755-774PubMedGoogle Scholar
  98. Liu ZX, Kaplowitz N (2006) Role of innate immunity in acetaminophen-induced hepatotoxicity. Expert Opin Drug Metab Toxicol 2:493-503PubMedGoogle Scholar
  99. Liu SF, Ye X, Malik AB (1999) Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents In vivo expression of proinflammatory genes. Circulation 100:1330-1337PubMedGoogle Scholar
  100. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8:500-508PubMedGoogle Scholar
  101. Louis H, Van Laethem JL, Wu W, Quertinmont E, Degraef C, Van den Berg K, Demols A, Goldman M, Le Moine O, Geerts A, Deviere J (1998) Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Hepatology 28:1607-1615PubMedGoogle Scholar
  102. Louis H, Le Moine O, Goldman M, Deviere J (2003) Modulation of liver injury by interleukin-10. Acta Gastroenterol Belg 66:7-14PubMedGoogle Scholar
  103. Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50:650-659PubMedGoogle Scholar
  104. Lue H, Kleemann R, Calandra T, Roger T, Bernhagen J (2002) Macrophage migration inhibitory factor (MIF): mechanisms of action and role in disease. Microbes Infect 4:449-460PubMedGoogle Scholar
  105. Lukacs NW, Strieter RM, Elner VM, Evanoff HL, Burdick M, Kunkel SL (1994) Intercellular adhesion molecule-1 mediates the expression of monocyte-derived MIP-1 alpha during monocyte-endothelial cell interactions. Blood 83:1174-1178PubMedGoogle Scholar
  106. Lukacs NW, Strieter RM, Elner V, Evanoff HL, Burdick MD, Kunkel SL (1995) Production of chemokines, interleukin-8 and monocyte chemoattractant protein-1, during monocyte: endothelial cell interactions. Blood 86:2767-2773PubMedGoogle Scholar
  107. Luster MI, Simeonova PP, Gallucci RM, Bruccoleri A, Blazka ME, Yucesoy B, Matheson JM (2000) The role of tumor necrosis factor alpha in chemical-induced hepatotoxicity. Ann N Y Acad Sci 919:214-220PubMedGoogle Scholar
  108. Ma XC, Xin J, Wang HX, Zhang T, Tu ZH (2003) Acute effects of huperzine A and tacrine on rat liver. Acta Pharmacol Sin 24:247-250PubMedGoogle Scholar
  109. Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, Senices M, Gill D, Dunussi-Joannopoulos K, Collins M, Nickerson-Nutter C, Fouser LA, Young DA (2008) IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 118:597-607PubMedGoogle Scholar
  110. Maltby J, Wright S, Bird G, Sheron N (1996) Chemokine levels in human liver homogenates: associations between GRO alpha and histopathological evidence of alcoholic hepatitis. Hepatology 24:1156-1160PubMedGoogle Scholar
  111. Masson MJ, Uetrecht JP (2004) Tolerance induced by low dose D-penicillamine in the brown Norway rat model of drug-induced autoimmunity is immune-mediated. Chem Res Toxicol 17:82-94PubMedGoogle Scholar
  112. Masubuchi Y, Bourdi M, Reilly TP, Graf ML, George JW, Pohl LR (2003) Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease. Biochem Biophys Res Commun 304:207-212PubMedGoogle Scholar
  113. Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991-1045PubMedGoogle Scholar
  114. Mayorga C, Pena RR, Blanca-Lopez N, Lopez S, Martin E, Torres MJ (2006) Monitoring the acute phase response in non-immediate allergic drug reactions. Curr Opin Allergy Clin Immunol 6:249-257PubMedGoogle Scholar
  115. Mitchell JA, Gillam EM, Stanley LA, Sim E (1990) Immunotoxic side-effects of drug therapy. Drug Saf 5:168-178PubMedGoogle Scholar
  116. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683-765PubMedGoogle Scholar
  117. Morio LA, Chiu H, Sprowles KA, Zhou P, Heck DE, Gordon MK, Laskin DL (2001) Distinct roles of tumor necrosis factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol Appl Pharmacol 172:44-51PubMedGoogle Scholar
  118. Murata H, Shimizu Y, Okada K, Higuchi K, Watanabe A (2003) Detection and analysis of intracytoplasmic cytokines in peripheral blood mononuclear cells in patients with drug-induced liver injury. J Hepatol 38:573-582PubMedGoogle Scholar
  119. Naisbitt DJ, Britschgi M, Wong G, Farrell J, Depta JP, Chadwick DW, Pichler WJ, Pirmohamed M, Park BK (2003) Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones. Mol Pharmacol 63:732-741PubMedGoogle Scholar
  120. Naisbitt DJ, Pirmohamed M, Park BK (2007) Immunological principles of T-cell-mediated adverse drug reactions in skin. Expert Opin Drug Saf 6:109-124PubMedGoogle Scholar
  121. Nassif A, Bensussan A, Boumsell L, Deniaud A, Moslehi H, Wolkenstein P, Bagot M, Roujeau JC (2004a) Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol 114:1209-1215PubMedGoogle Scholar
  122. Nassif A, Moslehi H, Le Gouvello S, Bagot M, Lyonnet L, Michel L, Boumsell L, Bensussan A, Roujeau JC (2004b) Evaluation of the potential role of cytokines in toxic epidermal necrolysis. J Invest Dermatol 123:850-855PubMedGoogle Scholar
  123. Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17:701-738PubMedGoogle Scholar
  124. Noguchi E, Shibasaki M, Arinami T, Takeda K, Yokouchi Y, Kawashima T, Yanagi H, Matsui A, Hamaguchi H (1998) Association of asthma and the interleukin-4 promoter gene in Japanese. Clin Exp Allergy 28:449-453PubMedGoogle Scholar
  125. Ochel M, Vohr HW, Pfeiffer C, Gleichmann E (1991) IL-4 is required for the IgE and IgG1 increase and IgG1 autoantibody formation in mice treated with mercuric chloride. J Immunol 146:3006-3011PubMedGoogle Scholar
  126. Olsen NJ (2004) Drug-induced autoimmunity. Best Pract Res Clin Rheumatol 18:677-688PubMedGoogle Scholar
  127. Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454-467PubMedGoogle Scholar
  128. Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A, Morse HC 3 rd, Liu C, Schwartzberg PL, Leonard WJ (2002) A critical role for IL-21 in regulating immunoglobulin production. Science 298:1630-1634PubMedGoogle Scholar
  129. Pai MP, Norenberg JP, Telepak RA, Sidney DS, Yang S (2005) Assessment of effective renal plasma flow, enzymuria, and cytokine release in healthy volunteers receiving a single dose of amphotericin B desoxycholate. Antimicrob Agents Chemother 49:3784-3788PubMedGoogle Scholar
  130. Paquet P, Nikkels A, Arrese JE, Vanderkelen A, Pierard GE (1994) Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis. Arch Dermatol 130:605-608PubMedGoogle Scholar
  131. Paul WE (2003) Fundamental immunology, 5th edn. Lippencott, Williams & Wilkins, PhiladelphiaGoogle Scholar
  132. Pessayre D (1995) Role of reactive metabolites in drug-induced hepatitis. J Hepatol 23(Suppl 1):16-24PubMedGoogle Scholar
  133. Pichler WJ (2006) Adverse side-effects to biological agents. Allergy 61:912-920PubMedGoogle Scholar
  134. Pichler WJ, Zanni M, von Greyerz S, Schnyder B, Mauri-Hellweg D, Wendland T (1997) High IL-5 production by human drug-specific T cell clones. Int Arch Allergy Immunol 113:177-180PubMedGoogle Scholar
  135. Piguet PF, Grau GE, Hauser C, Vassalli P (1991) Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J Exp Med 173:673-679PubMedGoogle Scholar
  136. Pirmohamed M, Lin K, Chadwick D, Park BK (2001) TNFalpha promoter region gene polymorphisms in carbamazepine-hypersensitive patients. Neurology 56:890-896PubMedGoogle Scholar
  137. Popovic M, Caswell JL, Mannargudi B, Shenton JM, Uetrecht JP (2006) Study of the sequence of events involved in nevirapine-induced skin rash in Brown Norway rats. Chem Res Toxicol 19:1205-1214PubMedGoogle Scholar
  138. Posadas SJ, Torres MJ, Mayorga C, Juarez C, Blanca M (2002) Gene expression levels of cytokine profile and cytotoxic markers in non-immediate reactions to drugs. Blood Cells Mol Dis 29:179-189PubMedGoogle Scholar
  139. Pumford NR, Myers TG, Davila JC, Highet RJ, Pohl LR (1993) Immunochemical detection of liver protein adducts of the nonsteroidal antiinflammatory drug diclofenac. Chem Res Toxicol 6:147-150PubMedGoogle Scholar
  140. Qasim FJ, Thiru S, Gillespie K (1997) Gold and D-penicillamine induce vasculitis and up-regulate mRNA for IL-4 in the Brown Norway rat: support for a role for Th2 cell activity. Clin Exp Immunol 108:438-445PubMedGoogle Scholar
  141. Qiao HL, Yang J, Zhang YW (2005) Relationships between specific serum IgE, cytokines and polymorphisms in the IL-4, IL-4Ralpha in patients with penicillins allergy. Allergy 60:1053-1059PubMedGoogle Scholar
  142. Qiao HL, Wen Q, Gao N, Tian X, Jia LJ (2007) Association of IL-10 level and IL-10 promoter SNPs with specific antibodies in penicillin-allergic patients. Eur J Clin Pharmacol 63:263-269PubMedGoogle Scholar
  143. Quddus J, Johnson KJ, Gavalchin J, Amento EP, Chrisp CE, Yung RL, Richardson BC (1993) Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J Clin Invest 92:38-53PubMedGoogle Scholar
  144. Ren X, Carpenter A, Hogaboam C, Colletti L (2003) Mitogenic properties of endogenous and pharmacological doses of macrophage inflammatory protein-2 after 70% hepatectomy in the mouse. Am J Pathol 163:563-570PubMedGoogle Scholar
  145. Reuss E, Fimmers R, Kruger A, Becker C, Rittner C, Hohler T (2002) Differential regulation of interleukin-10 production by genetic and environmental factors - a twin study. Genes Immun 3:407-413PubMedGoogle Scholar
  146. Rifkin IR, Leadbetter EA, Busconi L, Viglianti G, Marshak-Rothstein A (2005) Toll-like receptors, endogenous ligands, and systemic autoimmune disease. Immunol Rev 204:27-42PubMedGoogle Scholar
  147. Rogers PD, Jenkins JK, Chapman SW, Ndebele K, Chapman BA, Cleary JD (1998) Amphotericin B activation of human genes encoding for cytokines. J Infect Dis 178:1726-1733PubMedGoogle Scholar
  148. Rogers PD, Stiles JK, Chapman SW, Cleary JD (2000) Amphotericin B induces expression of genes encoding chemokines and cell adhesion molecules in the human monocytic cell line THP-1. J Infect Dis 182:1280-1283PubMedGoogle Scholar
  149. Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, Klinnert M, Borish L (1995) Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy 25(Suppl 2):74-78; discussion 95-96Google Scholar
  150. Roujeau JC (2006) Immune mechanisms in drug allergy. Allergol Int 55:27-33PubMedGoogle Scholar
  151. Roujeau JC, Stern RS (1994) Severe adverse cutaneous reactions to drugs. N Engl J Med 331:1272-1285PubMedGoogle Scholar
  152. Roychowdhury S, Svensson CK (2005) Mechanisms of drug-induced delayed-type hypersensitivity reactions in the skin. AAPS J 7:E834-E846PubMedGoogle Scholar
  153. Rubtsov YP, Rudensky AY (2007) TGFbeta signalling in control of T-cell-mediated self-reactivity. Nat Rev Immunol 7:443-453PubMedGoogle Scholar
  154. Salminen WF Jr, Voellmy R, Roberts SM (1997) Protection against hepatotoxicity by a single dose of amphetamine: the potential role of heat shock protein induction. Toxicol Appl Pharmacol 147:247-258PubMedGoogle Scholar
  155. Saoudi A, Kuhn J, Huygen K, de Kozak Y, Velu T, Goldman M, Druet P, Bellon B (1993) TH2 activated cells prevent experimental autoimmune uveoretinitis, a TH1-dependent autoimmune disease. Eur J Immunol 23:3096-3103PubMedGoogle Scholar
  156. Satoh J, Seino H, Abo T, Tanaka S, Shintani S, Ohta S, Tamura K, Sawai T, Nobunaga T, Oteki T et al (1989) Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice. J Clin Invest 84:1345-1348PubMedGoogle Scholar
  157. Sau K, Mambula SS, Latz E, Henneke P, Golenbock DT, Levitz SM (2003) The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor- and CD14-dependent mechanism. J Biol Chem 278:37561-37568PubMedGoogle Scholar
  158. Sayeh E, Uetrecht JP (2001) Factors that modify penicillamine-induced autoimmunity in Brown Norway rats: failure of the Th1/Th2 paradigm. Toxicology 163:195-211PubMedGoogle Scholar
  159. Seder RA, Ahmed R (2003) Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol 4:835-842PubMedGoogle Scholar
  160. Segal R, Dayan M, Zinger H, Mozes E (2001) Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNFalpha monoclonal antibody and by pentoxiphylline. Lupus 10:23-31PubMedGoogle Scholar
  161. Selzner M, Camargo CA, Clavien PA (1999) Ischemia impairs liver regeneration after major tissue loss in rodents: protective effects of interleukin-6. Hepatology 30:469-475PubMedGoogle Scholar
  162. Shaw PJ, Hopfensperger MJ, Ganey PE, Roth RA (2007) Lipopolysaccharide and trovafloxacin coexposure in mice causes idiosyncrasy-like liver injury dependent on tumor necrosis factor-alpha. Toxicol Sci 100:259-266PubMedGoogle Scholar
  163. Shenton JM, Popovic M, Chen J, Masson MJ, Uetrecht JP (2005) Evidence of an immune-mediated mechanism for an idiosyncratic nevirapine-induced reaction in the female Brown Norway rat. Chem Res Toxicol 18:1799-1813PubMedGoogle Scholar
  164. Simpson KJ, Lukacs NW, McGregor AH, Harrison DJ, Strieter RM, Kunkel SL (2000) Inhibition of tumour necrosis factor alpha does not prevent experimental paracetamol-induced hepatic necrosis. J Pathol 190:489-494PubMedGoogle Scholar
  165. Sobel DO, Ewel CH, Zeligs B, Abbassi V, Rossio J, Bellanti JA (1994) Poly I:C induction of alpha-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships. Diabetes 43:518-522PubMedGoogle Scholar
  166. Stachlewitz RF, Arteel GE, Raleigh JA, Connor HD, Mason RP, Thurman RG (1997) Development and characterization of a new model of tacrine-induced hepatotoxicity: role of the sympathetic nervous system and hypoxia-reoxygenation. J Pharmacol Exp Ther 282:1591-1599PubMedGoogle Scholar
  167. Stordeur P, Goldman M (1998) Interleukin-10 as a regulatory cytokine induced by cellular stress: molecular aspects. Int Rev Immunol 16:501-522PubMedGoogle Scholar
  168. Sullivan JR, Shear NH (2001) The drug hypersensitivity syndrome: what is the pathogenesis? Arch Dermatol 137:357-364PubMedGoogle Scholar
  169. Sun Y, Tokushige K, Isono E, Yamauchi K, Obata H (1992) Elevated serum interleukin-6 levels in patients with acute hepatitis. J Clin Immunol 12:197-200PubMedGoogle Scholar
  170. Taub R (2003) Hepatoprotection via the IL-6/Stat3 pathway. J Clin Invest 112:978-980PubMedGoogle Scholar
  171. Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275:18138-18144PubMedGoogle Scholar
  172. Teunissen MB, Koomen CW, de Waal Malefyt R, Wierenga EA, Bos JD (1998) Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol 111:645-649PubMedGoogle Scholar
  173. Tournade H, Pelletier L, Pasquier R, Vial MC, Mandet C, Druet P (1990) D-penicillamine-induced autoimmunity in Brown-Norway rats. Similarities with HgCl2-induced autoimmunity. J Immunol 144:2985-2991PubMedGoogle Scholar
  174. Tracey KJ, Cerami A (1993) Tumor necrosis factor, other cytokines and disease. Annu Rev Cell Biol 9:317-343PubMedGoogle Scholar
  175. Tukov FF, Luyendyk JP, Ganey PE, Roth RA (2007) The role of tumor necrosis factor alpha in lipopolysaccharide/ranitidine-induced inflammatory liver injury. Toxicol Sci 100:267-280PubMedGoogle Scholar
  176. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1-8PubMedGoogle Scholar
  177. Uetrecht JP (1999) New concepts in immunology relevant to idiosyncratic drug reactions: the “danger hypothesis” and innate immune system. Chem Res Toxicol 12:387-395PubMedGoogle Scholar
  178. Ungo JR, Jones D, Ashkin D, Hollender ES, Bernstein D, Albanese AP, Pitchenik AE (1998) Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus. Am J Respir Crit Care Med 157:1871-1876PubMedGoogle Scholar
  179. Vandebriel RJ, Van Och FM, van Loveren H (2005) In vitro assessment of sensitizing activity of low molecular weight compounds. Toxicol Appl Pharmacol 207:142-148PubMedGoogle Scholar
  180. Villada G, Roujeau JC, Clerici T, Bourgault I, Revuz J (1992) Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases. Arch Dermatol 128:50-53PubMedGoogle Scholar
  181. Wang YH, Liu YJ (2008) The IL-17 cytokine family and their role in allergic inflammation. Curr Opin Immunol 20:697-702PubMedGoogle Scholar
  182. Weber RW (2004) Adverse reactions to biological modifiers. Curr Opin Allergy Clin Immunol 4:277-283PubMedGoogle Scholar
  183. Weber LW, Boll M, Stampfl A (2003) Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 33:105-136PubMedGoogle Scholar
  184. Williams AM, Langley PG, Osei-Hwediah J, Wendon JA, Hughes RD (2003) Hyaluronic acid and endothelial damage due to paracetamol-induced hepatotoxicity. Liver Int 23:110-115PubMedGoogle Scholar
  185. Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K, Volk HD, Sterry W, Sabat R (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36:1309-1323PubMedGoogle Scholar
  186. Wood N, Bourque K, Donaldson DD, Collins M, Vercelli D, Goldman SJ, Kasaian MT (2004) IL-21 effects on human IgE production in response to IL-4 or IL-13. Cell Immunol 231:133-145PubMedGoogle Scholar
  187. Xu H, DiIulio NA, Fairchild RL (1996) T cell populations primed by hapten sensitization in contact sensitivity are distinguished by polarized patterns of cytokine production: interferon gamma-producing (Tc1) effector CD8+ T cells and interleukin (Il) 4/Il-10-producing (Th2) negative regulatory CD4+ T cells. J Exp Med 183:1001-1012PubMedGoogle Scholar
  188. Yamada Y, Fausto N (1998) Deficient liver regeneration after carbon tetrachloride injury in mice lacking type 1 but not type 2 tumor necrosis factor receptor. Am J Pathol 152:1577-1589PubMedGoogle Scholar
  189. Yamano T, Higashi T, Nouso K, Nakatsukasa H, Kariyama K, Yumoto E, Kobayashi Y, Yamamoto K, Iwagaki H, Yagi T, Tanimoto T, Kurimoto M, Tanaka N, Tsuji T (2000) Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis. Clin Exp Immunol 122:227-231PubMedGoogle Scholar
  190. Yang J, Qiao HL, Dong ZM (2005) Polymorphisms of IL-13 and IL-4-IL-13-SNPs in patients with penicillin allergies. Eur J Clin Pharmacol 61:803-809PubMedGoogle Scholar
  191. Yee SB, Bourdi M, Masson MJ, Pohl LR (2007) Hepatoprotective role of endogenous interleukin-13 in a murine model of acetaminophen-induced liver disease. Chem Res Toxicol 20:734-744PubMedGoogle Scholar
  192. You Q, Cheng L, Reilly TP, Wegmann D, Ju C (2006) Role of neutrophils in a mouse model of halothane-induced liver injury. Hepatology 44:1421-1431PubMedGoogle Scholar
  193. Yung RL, Quddus J, Chrisp CE, Johnson KJ, Richardson BC (1995) Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J Immunol 154:3025-3035PubMedGoogle Scholar
  194. Zamara E, Galastri S, Aleffi S, Petrai I, Aragno M, Mastrocola R, Novo E, Bertolani C, Milani S, Vizzutti F, Vercelli A, Pinzani M, Laffi G, LaVilla G, Parola M, Marra F (2007) Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice. J Hepatol 46:230-238PubMedGoogle Scholar
  195. Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Karow M, Flavell RA (2007) Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27:647-659PubMedGoogle Scholar
  196. Zisman DA, Kunkel SL, Strieter RM, Tsai WC, Bucknell K, Wilkowski J, Standiford TJ (1997) MCP-1 protects mice in lethal endotoxemia. J Clin Invest 99:2832-2836PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Mary Jane Masson
    • 1
    Email author
  • Lindsay A. Collins
  • Lance R. Pohl
  1. 1.Laboratory of Molecular and Cellular Toxicology, Laboratory of Molecular ImmunologyNational Heart, Lung, and Blood Institute, National Institutes of HealthBethesdaUSA

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