Skip to main content
SpringerLink
Log in

Cyclosporin A

  • Chapter
Strategies for Immunointerventions in Dermatology

  • 90 Accesses

Abstract

CsA (ciclosporin, cyclosporine, Sandimmune, SIM) is derived from the fungus Tolypo- cladium inflatum and is a neutral, lipophilic, cyclic undecapeptide that has a molecular weight of 1203. Borel and colleagues [4] showed CsA to be a powerful inhibitor of T cell activation induced by mitogen or mixed lymphocyte reaction (MLR). They also observed the concentration of CsA needed to inhibit T cell activation was noncytotoxic, reversible, and did not block the proliferation of other cell types at low concentrations, suggesting it might make a useful immunosuppressant. This prediction was accurate, as CsA is today the first-line drug for preventing allograft rejection in organ and bone marrow transplant recipients. Additionally, CsA has been used in treating autoimmune diseases such as systemic lupus erythematosus (SLE), myasthenia gravis, adult-onset and juvenile diabetes, and rheumatoid arthritis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barthelemy H, Fraapaz A, Cambazard F, Mauduit G, Rouchouse B, Kanitakis J, Souteyrand P, Claudy AL, Thivolet J (1988) Treatment of nine cases of pemphigus vulgaris with cyclosporine. J Am Acad Dermatol 18:1262–1266.

    Article  PubMed  CAS  Google Scholar 

  2. Batiuk TD, Pazderka F, Enns J, DeCastro L, Halloran PF (1995) Cyclosporine inhibition of calcineurin activity in human leukocytes in vivo is rapidly reversible. J Clin Invest 96:1254–1260.

    Article  PubMed  CAS  Google Scholar 

  3. Bierer BE, Hollander G, Fruman D, Burakoff SJ (1993) Cyclosporin A and FK506: molecular mechanisms of immunosuppression and probes for transplantation biology. Curr Opin Immunol 5:763–773.

    Article  PubMed  CAS  Google Scholar 

  4. Borel JF, Feurer C, Gubler HU, Stahelin H (1976) Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions 6:468–475.

    Article  PubMed  CAS  Google Scholar 

  5. Borel JF, Feurer C, Magnee C, Stahelin H (1977) Effects of the new antilymphocy tic peptide cyclosporin A in animals. Immunology 32:1017–1025.

    PubMed  CAS  Google Scholar 

  6. Braun W, Kallen J, Mikol V, Walkinshaw MD, Wuthrich K (1995) Three-dimensional structure and actions of immunosuppressants and their immunophilins. FASEB J 9:63–72.

    PubMed  CAS  Google Scholar 

  7. Burns MK, Ellis, CN, Eisen D, Duell E, Griffiths CEM, Annesley TM, Hamilton TA, Birnbaum JE, Voorhees JJ (1992) Intralesional cyclosporine for psoriasis. Arch Dermatol 128:786–790.

    Article  PubMed  CAS  Google Scholar 

  8. Camp RDR, Reitamo S, Friedman PS, Ho V, Heule F (1993) Cyclosporin A in severe, therapy-resistant atopic dermatitis: report of an international workshop, April 1993. Br J Dermatol 129:217–220.

    Article  PubMed  CAS  Google Scholar 

  9. Campbell PM, Pimm, J, Ramassar V, Halloran PF (1996) identification of a calcium-inducible, cyclosporine-sensitive element in the IFNy promoter that is a potential NFAT binding site. Transplantation 61:933–939.

    Article  PubMed  CAS  Google Scholar 

  10. Chatellard-Gruaz D, Saurat J-H, Siegenthaler G (1994) Differential expression of cyclophilin isoforms during keratinocyte differentiation. Biochem J 303:863–867.

    PubMed  CAS  Google Scholar 

  11. Cirillo R, Triggiana M, Siri L, Ciccarelli A, Pettit GR, Condorelli M, Marone G (1990) Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. J Immunol 150:2591–2598.

    Google Scholar 

  12. Clipstone NA, Crabtree GR (1992) Identification ot calcmeurin as a key signalling enzyme in T-lymphocyte activation. Nature 357:695–697.

    Article  PubMed  CAS  Google Scholar 

  13. Cockerill PN, Shannon MF, Bert AG, Ryan GR, Vadas MA, (1993) The granulocyte-macrophage colony-stimulating factor/interleukin 3 locus is regulated by an inducible cyclosporin A-sen- sitive enhancer. Proc Natl Acad Sei USA 90:2466–2470.

    Article  CAS  Google Scholar 

  14. Cooper KD (1994) Atopic dermatitis: recent trends in pathogenesis and therapy. J Invest Dermatol 102:128–137.

    Article  PubMed  CAS  Google Scholar 

  15. Correia O, Polonia J, Nunes IP, Resende C, Delgado I (1992) Severe acute form of adult dermatomyositis treated with cyclosporine. Int J Dermatol 31:517–519.

    Article  PubMed  CAS  Google Scholar 

  16. Crow LL, Finkle JP, Gammon WR% Woodley DT (1988) Clearing of epidermolysis bullosa acquisita with cyclosporine. J Am Acad Dermatol 19:937–942.

    Article  PubMed  CAS  Google Scholar 

  17. Duncan JI (1994) Differential inhibition of cutaneous T-cell-mediated reactions and epidermal cell proliferation by cyclosporin A, FK-506, and rapamycin. J invest Dermatol 102:84–88.

    Article  PubMed  CAS  Google Scholar 

  18. Duncan JI, Wakeel RA, Winfield A J, Ormerod AD, Thomson AW (1993) Immunomodulation of psoriasis with a topical cyclosporin A formulation. Acta Derm Venereol(Stockh) 73:84–87

    Google Scholar 

  19. Eisen D, Griffiths CEM, Ellis CN, Nickoloff BJ, Voorhees JJ (1990) Cyclosporin wash for oral lichen planus. Lancet 335:535–536.

    Article  PubMed  CAS  Google Scholar 

  20. Elder JT, Hammerberg C, Cooper KD, Kojima T, Nair RP, Ellis CN, Voorhees JJ (1993) Cyclosporin A rapidly inhibits epidermal cytokine expression in psoriasis lesions, but not in cytokine-stimulated cultured keratinocytes. J Invest Dermatol 101:761–766.

    Article  PubMed  CAS  Google Scholar 

  21. Ellis CN, Gorsulowsky DC, Hamilton TA, Billings JK, Brown MD, Headington JT, Cooper KD, Baadsgaard O, Duell EA, Annesley TM, Turcotte IG, Voorhees JJ (1986) Cyclosporine improves psoriasis in a double-blind study. JAMA 256:3110–3116.

    Article  PubMed  CAS  Google Scholar 

  22. Ellis CN, Fradin MS, Messana IM, Brown MD, Siegel MT, Hartley AH, Rocher LL, Wheeler S, Hamilton TA, Parrish TG, Ellis Madu M, Duell E, Annesley TM, Cooper KD, Voorhees JJ (1991) Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial. N Engl J Med 324:277–284.

    Article  PubMed  CAS  Google Scholar 

  23. Favre H, Miescher PA, Lemoine R (1994) Use of cyclosporine in the treatment of autoimmune disorders. Transplant Proc 26:3194–3196.

    PubMed  CAS  Google Scholar 

  24. Fedi MC, Quercetani R, Lotti T (1993) Recalcitrant pyoderma gangrenosum responsive to cyclosporine. Int J Dermatol 32:119.

    Article  PubMed  CAS  Google Scholar 

  25. Ferns G, Reidy M, Ross R (1990) Vascular effects of cyclosporin A in vivo and in vitro. Am J Pathol 137:403–413.

    PubMed  CAS  Google Scholar 

  26. Fischer G, Wittman-Liebold B, Lang K, Kiefhaber T, Schmid FX (1989 Cyclophilin and peptidyl-prolyl cis-trans isomerase are probablv identical proteins. Nature 337:476–478.

    Article  PubMed  CAS  Google Scholar 

  27. Fisher GJ, Duell EA, Nickoloff BJ, Annesley TM, Kowalke JK, Ellis CN, Voorhees JJ (1988) Levels of cyclosporine in epidermis of treated psoriasis patients differentially inhibit growth of keratinocytes cultured in serum free versus serum containing media. ■ Invest Dermatol 91:142–146.

    Google Scholar 

  28. Frances C, BoisnicS, Etienne S, Szpirglas H (1988) Effect of the local application of cyclosporin A on chronic erosive lichen planus of the oral cavity Dermatologica 177:194–195.

    CAS  Google Scholar 

  29. Furue M, Gaspari AA, Katz SI (1988) The effect of cyclosporin A on epidermal cells. II. Cyclosporin A inhibits proliferation of normal and transformed keratinocytes. J Invest Dermatol 90:796–800.

    Google Scholar 

  30. Gebhart W, Schmidt JB, Schemper M, Spona J, Kopsa H, Zazgornik S (1986) Cyclosporin-A-in- duced hair growth in human renal allograft recipients and alopecia areata. Arch Dermatol Res 278:238–240.

    Article  PubMed  CAS  Google Scholar 

  31. Goldfeld A McCaffrey PG,Strominger J,Rao A (1993) Identification of a novel cyclosporin- sensitive element in the human tumour necrosis factor-α gene promoter.J Exp Med 178: 1365–1379

    Google Scholar 

  32. Gottlieb AB, Grossman RM, Khandke L, Carter DM, Sehgal PB, Fu SM, Granelli-Piperno A, Rivas M, Barazani L, Krueger JG (1992) Studies of the effect of cyclosporine in psoriasis in vivo: combined effects on activated T lymphocytes and epidermal regenerative maturation. J Invest Dermatol 98:302–309.

    Article  PubMed  CAS  Google Scholar 

  33. Graham R (1994) Cyclosporine: mechanisms of action and toxicity. Cleve Clin J Med 61:308–313.

    PubMed  CAS  Google Scholar 

  34. Granelli-Piperno A, Keane M, Steinman RM (1988) Evidence that cyclosporin inhibits cell- mediated immunity at the level of the T lymphocyte rather than the accessory cell. Transplantation 46:53S–60S.

    Article  PubMed  CAS  Google Scholar 

  35. Griffiths CEM, Fisher GJ, Harding MW, Elder JT, Voorhees JJ (1990) Cyclophilin content of normal and psoriatic epidermis. J Invest Dermatol 94:436–440.

    Article  PubMed  CAS  Google Scholar 

  36. Grossman RM, Chevret S, Abi-Rachad J, Blanchet F, Dubertret L (1996) Long-term safety of cyclosporine in the treatment of psoriasis. Arch Dermatol 132:623–629.

    Article  PubMed  CAS  Google Scholar 

  37. Gupta AK Ellis CN, Tellner DC, Voorhees JJ (1988) Cyclosporine A in the treatment of severe alopecia areata. Transplant Proc 20:105–108.

    PubMed  CAS  Google Scholar 

  38. Gupta AK, Ellis CN, Cooper KD, Nickoloff BJ, Ho VC, Chan LS, Hamilton TA, Tellner DC, Griffiths CEM, Voorhees JJ (1990) Oral cyclosporine for the treatment of alopecia areata: a clinical and immunohistochemical analysis. J Am Acad Dermatol 22:242–250.

    Article  PubMed  CAS  Google Scholar 

  39. Hess AD, Tutschka PJ (1981) Effect of cyclosporin A on human lymphocyte responses in vitro. I. CsA allows for the expression of alloantigen-activated suppressor cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in the MLR. J Immunol 124:2601–2608.

    Google Scholar 

  40. Ho VC, Zloty DM (1993) Immunosuppressive agents in dermatology. Dermatol Clin 11:73–85.

    Article  PubMed  CAS  Google Scholar 

  41. Ho VC, Gupta AK, Ellis CN, Cooper KD, Nickoloff BJ, Voorhees JJ (1989) Cyclosporine in lamellar ichthyosis. Arch Dermatol 125:511–514.

    Article  PubMed  CAS  Google Scholar 

  42. Ho VC, Gupta AK, Ellis CN, Nickoloff BJ, Voorhees JJ (1990) Treatment of severe lichen planus with cyclosporine. J Am Acad Dermatol 22:64–68.

    Article  PubMed  CAS  Google Scholar 

  43. Ippoliti G, Miori L, Negri M, Rovati B, Lorenzutti F, Zerbinati N, Rabbiosi G (1994) Cyclosporine in treatment of progressive systemic sclerosis: clinical and immunologic findings. Transplant Proc 26:3117–3118.

    PubMed  CAS  Google Scholar 

  44. June CH, Ledbetter JA, Gillespie MM, Lindstein T, Thompson CB (1987) T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol 7:4472–4481.

    PubMed  CAS  Google Scholar 

  45. Kahan BD,VanBuren CT,Nierberger W (1983) Cyclosporine: pharmokinetics, metabolism and drug interaction. Transplant Proc 15:2409–2412

    Google Scholar 

  46. Kato N, Halprin KM, Taylor JR (1987) Cyclosporin A does not inhibit epidermal cell growth at therapeutic levels. J Invest Dermatol 88:52–54.

    Article  PubMed  CAS  Google Scholar 

  47. Kauver AB, Stiller MJ (1994) Cyclosporine in dermatology: pharmacology and clinical use. Int J Dermatol 33:86–96.

    Article  Google Scholar 

  48. Krupp P, Monka C (1990) Side-effect profile of cyclosporin A in patients treated for psoriasis. Br J Dermatol 122 [Suppl 36]:47–56.

    Article  PubMed  Google Scholar 

  49. Lay ton AM, Cunliffe WJ (1990) Clearing of epidermolysis bullosa acquisita with cyclosporine. J Am Acad Dermatol 22:535–536.

    Article  PubMed  CAS  Google Scholar 

  50. Liu J (1993) FK506 and cyclosporin, molecular probes for studying intracellular signal transduction. Immunol Today 14:290–295.

    Article  PubMed  CAS  Google Scholar 

  51. Liu J, Farmer JDJ, Lane WS, Friedman J, Weissman I, Schreiber SL (1991) Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66:807–815.

    Article  PubMed  CAS  Google Scholar 

  52. Matis WL, Ellis CN, Griffiths CEM, Lazarus GS (1992) Treatment of pyoderma gangrenosum with cyclosporine. Arch Dermatol 128:1519–1529.

    Article  Google Scholar 

  53. McCaffrey PG, Perrino BA, Soderling TR, Rao A (1993) NF-ATp, a T lymphocyte DNA-binding protein that is a target for calcineurin and immunosuppressive drugs. J Biol Chem 268:3747–3752.

    PubMed  CAS  Google Scholar 

  54. Mueller W, Herrmann B (1979) Cyclosporin A for psoriasis. N Engl J Med 301:555.

    PubMed  CAS  Google Scholar 

  55. Munro CS, Higgins EM, Marks JM, Daly BM, Friedman PS, Shuster S (1991) Cyclosporin A in atopic dermatitis: therapeutic response is dissociated from affects on allergic reactions. Br J Dermatol 124:43–48.

    Article  PubMed  CAS  Google Scholar 

  56. Nickoloff B (1991) The cytokine network in psoriasis. Arch Dermatol 127:871–884.

    Article  PubMed  CAS  Google Scholar 

  57. Nickoloff BJ, Fisher GJ, Mitra RS, Voorhess JJ (1988) Additive and synergistic antiproliferative effect of cyclosporin A and gamma interferon on cultured human keratinoc vtes. Am J Pathol 131:12–18.

    PubMed  CAS  Google Scholar 

  58. Noble S, Markham A (1995) Cyclosporin. A review of the pharmokinetic properties, clinical efficacy and tolerability of a microemulsion-based formulation (Neoral). Drugs 50:924–41.

    Article  PubMed  CAS  Google Scholar 

  59. Rao A (1995) NFATp, a cyclosporin-sensitive transcription factor implicated in cytokine gene induction. J Leukoc Biol 57:536–542.

    PubMed  CAS  Google Scholar 

  60. SchmittEC, PigattoPD, Boneschi V, Bubola D, Finzi AF (1993) Pyoderma gangrenosum treated with low-dose cyclosporin, Br J Dermatol 128:230–231.

    Article  PubMed  Google Scholar 

  61. Schrieber SL, Crabtree GR (1992) The mechanism of action of cyclosporin A and FK506. Immunol Today 13:136–142.

    Article  Google Scholar 

  62. SharpeGR Fisher C (1990) Time-dependent inhibition of growth of human keratinocytes and fibroblasts by cyclosporin A: effect on keratinocytes at therapeutic blood levels. Br J Dermatol 123:207–213.

    Article  PubMed  CAS  Google Scholar 

  63. Sieg P, Von Domarus H, Von Zitzewitz V, Iven H, Farber L (1995) Topical cyclosporin in oral lichen planus: a controlled, randomized, prospective trial. Br I Dermatol 132:790–794.

    Article  CAS  Google Scholar 

  64. Sigal NH, Dumont FJ (1992) Cyclosporin A, FK-506, and rapamycin: pharmacological probes of lymphocyte signal transduction. Annu Rev Immunol 10:519–560.

    Article  PubMed  CAS  Google Scholar 

  65. Stellato C, de Paulis A, Ciccarelli A, Cirillo R, Patella V, Casolaro V, Marone U (1992) Anti-inflammatory effect of cyclosporin A on human skin mast cells. J Invest Dermatol 800–804

    Google Scholar 

  66. Takahashi N, HayanoT, Suzuki M (1989) Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337:473–475.

    Article  PubMed  CAS  Google Scholar 

  67. Taniguchi S, Kono T, Ishii M, Ha mad a T (1995) Effects of cyclosporin and ultraviolet radiation on growth and ornithine decarboxylase activity in cultured human epidermal keratinocytes. Br J Dermatol 132:703–709.

    Article  PubMed  CAS  Google Scholar 

  68. Thivolet J, Barthelemy H, Rigot Muller G, Bendelac A (1985) Effects of cyclosporin on bullous pemphigoid and pemphigus. Lancet 1:334–335.

    Article  PubMed  CAS  Google Scholar 

  69. Urabe A, Kaniakis J, Viae J, Thivolet J (1989) Cyclosporin A inhibits directly in vivo kerati- nocyte proliferation of living human skin.J Invest Dermatol 92:755–757

    Google Scholar 

  70. Van Joost T, Heule F, Korstanje M, Van Den Broek MJTB, Stenveld Hi, Van Vloten WA (1994) Cyclosporin in atopic dermatitis: a multicentre placebo-controlled stud v. Br J Dermatol 130:634–640.

    Article  PubMed  Google Scholar 

  71. Wang DZ,McCaffrey PG,Rao A (1995) The cyclosporin sensitive transcrip: on factor NFATp is expressed in several classes ot cells in the immune system. Ann N Y Acad Sci 766:182–194.

    Article  PubMed  CAS  Google Scholar 

  72. Wicker LS , Boltz RC, Matt V Nichols FA,Peterson LB, Sigal NH (1990)Suppression of B-cell activation by cyclosporin-A, FK506, and rapamvcin. Eur J Immunol 20:2277–2283

    Google Scholar 

  73. Won Y-H, Sauder DN, Mckenzie RC (1994) Cyclosporin A inhibits keratinov te cytokine gene expression. Br J Dermatol 130:312–319.

    Article  PubMed  CAS  Google Scholar 

  74. Wong RL, Winslow CM, Cooper KI (1993) The mechanisms of action of cyclosporin A in the treatment of psoriasis. Immunol Today 14:69–74.

    Article  PubMed  CAS  Google Scholar 

  75. Zav’yalov VP, Denesyuk A1. Lundell J, Korpela I (1995) Some new aspects of molecular mechanisms of cyclosporin A effect on immune response, APMIS 103:401–415.

    Article  PubMed  Google Scholar 

Download references

Authors
  1. T. Wrone-Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. J. Nickoloff
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091, Zurich, Switzerland

    Günter Burg M.D. (Chairman) (Chairman)

  2. Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091, Zurich, Switzerland

    Reinhard G. Dummer M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Wrone-Smith, T., Nickoloff, B.J. (1997). Cyclosporin A. In: Burg, G., Dummer, R.G. (eds) Strategies for Immunointerventions in Dermatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60752-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60752-3_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64539-6

  • Online ISBN: 978-3-642-60752-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation