Summary
Cyclosporin A is a cyclical polypeptide of 11 amino acids, one of which is unique to the cyclosporins. First isolated as an antifungal agent, it has been shown to have marked immunomodulatory properties. These properties have meant that the drug can be used as an immunosuppressant to prevent the rejection of transplants, both of organs and bone marrows, as well as in the control of autoimmune diseases. It has already been shown to have a major clinical impact in the transplantation of kidneys, pancreas, liver, hearts, heart and lung and both compatible and incompatible bone marrow grafts. The drug acts by inhibiting that part of the immune system which relies on T cell proliferation, probably by interference with second signal controls.
The clinical results so far achieved with cyclosporin A indicate that it has an important part to play in the future of immunosuppression. With better, more reliable, immunosuppressive control, the possibility exists that transplantation of immunologically more susceptible organs could become a routine procedure providing a treatment to patient populations whose conditions had previously been considered incurable.
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Baldwin III, W.M.; Hutchinson, I.F.; Meijer, C.J.L.M. and Tilney, N.L.: Marked decrease in medullary thymocytes and splenic T lymphocytes after cyclosporin A treatment. Transplantation 31: 117 (1981).
Borel, J.F.: Comparative study of in vitro and in vivo drug effects on cell mediated cytotoxicity. Immunology 31: 631 (1976).
Borel, J.F.; Feurer, C.; Gubler, H.U. and Stahelin, H.: Biological effects of cyclosporin A, a new anti-lymphocytic agent. Agents and Actions 6: 468 (1976).
Borel, J.F.; Feurer, C.; Magnee, C. and Stahelin, H.: Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology 32: 1017 (1977).
Borel, J.F. and Weisinger, D.: Effects of cyclosporin A on murine lymphoid cells in regulatory mechanisms in lymphocyte activation. Proceedings of the 11th Leucocyte Culture Conference, pp.716–718 (Academic Press, London 1977).
Borel, J.F. and Weisinger, D.: Studies on the mechanism of action of cyclosporin A. Brit. J. Pharm. 66: 66 (1979).
Borel, J.F.; Weisinger, D. and Gubler, H.U.: Effects of the antilymphocytic peptide cyclosporin A in chronic inflammation. European Journal of Rheumatology and Inflammation 1: 237 (1978).
Burckhardt, J.J. and Guggenheim, B.: Cyclosporin A: In vivo and in vitro suppression of rat T-lymphocyte function. Immunology 36: 753 (1979).
Calne, R.Y.: Inhibition of the rejection of renal homografts by purine analogues. Transplantation Bulletin 28: 65 (1961).
Calne, R.Y.: Pharmacological immunosuppression in clinical organ grafting. Clinical and Experimental Immunology 35: 1 (1979).
Calne, R.Y.; Rolles, K. and White, D.J.G.: Cyclosporin A in clinical organ grafting. Transplantation Proceedings 13: 349 (1981a).
Calne, R.Y. and White, D.J.G.: Cyclosporin A — a powerful immunosuppressant in dogs with renal allografts. IRCS Journal of Medical Science 5: 280 (1977).
Calne, R.Y.; White, D.J.G.; Evans, D.B.; Thiru, S.; Henderson, R.G.; Hamilton, D.V.; Rolles, K.; McMaster, P.; Duffy, T.J.; MacDougal, B.R.D. and Williams, R.: Cyclosporin A in cadaveric organ transplantation. British Medical Journal 282: 934 (1981b).
Calne, R.Y.; White, D.J.G.; Rolles, K.; Smith, D.P. and Herbertson, B.M.: Prolonged survival of pig orthotopic heart grafts with cyclosporin A. Lancet 1: 1183 (1978a).
Calne, R.Y.; White, D.J.G.; Thiru, S.; Evans, D.B.; McMaster, P.; Dunn, D.C.; Craddock, G.N.; Pentlow, B.D. and Rolles, K.: Cyclosporin A in patients receiving renal allografts from cadaveric donors. Lancet 2: 1323 (1978b).
Calne, R.Y.; Williams, R.; Lindop, M.; Farman, J.V.; Tolley, M.E.; Rolles, K.; MacDougall, B.; Neuberger, J.; Wyke, R.J.; Raftery, A.T.; Duffy, T.J.; Wight, D.G.D. and White, D.J.G.: Improved survival after orthotopic liver grafting. British Medical Journal 283: 115 (1981c).
Cosimi, A.B.; Shield, C.F.; Peters, C. et al.: Prolongation of allograft survival by cyclosporin A. Surgical Forum 30: 287 (1978).
Dreyfuss, M.; Haerri, E.; Hoffman, H.; Kobel, H.; Pache, W. and Tscherter, H.: Cyclosporin A and C. New metabolites from Trichoderma polysporum. European Journal of Applied Microbiology 3: 125 (1976).
Dunn, D.C.; White, D.J.G. and Herbertson, B.M.: Persistent nonspecific immunosuppression after a course of cyclosporin A. Transplantation 29: 349 (1980).
Editorial: Heart and lung transplants may herald a new era. Journal of the American Medical Association 245: 1397 (1981).
Gordon, M.Y. and Singer, J.W.: Selective effects of cyclosporin A on colony forming lymphoid and myeloid cells in man. Nature 279: 433 (1979).
Green, C.J. and Allison, A.C.: Extensive prolongation of rabbit kidney allograft survival after short term cyclosporin A treatment. Lancet 1: 1182 (1978).
Herman, B. and Mueller, W.: Therapy of chronic rheumatoid arthritis with cyclosporin A. Aktuelle Rheumatologie p. 173 (1979).
Human Renal Transplant Registry: 13th Report. Transplantation Proceedings 9: whole issue (1977).
Hume, D.M.; Merrill, J.P. and Miller, B.F.: Homologous transplantation of human kidneys. Journal of Clinical Investigation 31: 640 (1952).
Kahan, B.D.: Cosmas and Damian in the 20th Century? New England Journal of Medicine 305: 280 (1981).
Keown, P.A.; Stiller, C.R.; Ulan, R.A.; Sinclair, N.R.; Rankin, C.; Carruthers, G. and Wall, W.J.: Inhibition of the donor-specific immune response by Cyclosporin A following renal transplantation. Transplantation Proceedings XIII (No, 3): 1669–1672 (1981).
Kostakis, A.J.; White, D.J.G. and Calne, R.Y.: Toxic effects in the use of cyclosporin A in alcoholic solution as an immunosuppressant of rat heart allografts. IRCS Journal of Medical Science 5: 243 (1977a).
Kostakis, A.J.; White, D.J.G. and Calne, R.Y.: Prolongation of rat heart allograft survival by cyclosporin A. IRCS Journal of Medical Science 5: 595 (1977b).
Kunkl, A. and Klaus, G.G.B.: Selective effects of cyclosporin A on functional B cell subsets in mouse. Journal of Immunology 125: 2526 (1980).
Larsson, E.L.: Cyclosporin A and dexamethasone suppress T cell responses by selectively acting at distinct sites of the triggering process. Journal of Immunology 124: 2828 (1980).
Leapman, S.B.; Filo, R.S.; Smith, E.J. and Smith, P.G.: Effects of cyclosporin A on the generation of memory cells in vitro. Transplantation Proceedings 12: 245 (1980).
Lindsey, N.J.; Harris, K.R. and Norman, H.B.: The effect of cyclosporin A on the primary and secondary immune response in the rabbit. Trans. Proc. 12: 252 (1980).
McMaster, P.; Procyshyn, A. and Calne, R.Y.: Prolongation of canine pancreas allografts with cyclosporin A. Transplantation Proceedings 12: 275 (1980).
Mueller, W. and Herman, B.: Cyclosporin A for psoriasis. New England Journal of Medicine 301: 555 (1979).
Petcher, T.J.; Weber, H.P. and Ruegger, A.: Crystal and molecular structure of an iodo-derivative of the cyclical undecapeptide cyclosporin A. Helvetica Chimica Acta 59: 1480 (1976).
Powles, R.L.; Barrett, A.J. and Clink, H.: Cyclosporin A for the treatment of graft versus host disease in man. Lancet 2: 1327 (1978).
Powles, R.L.; Clink, H.M.; Spence, D.; Morgenstern, G.; Watson, J.G.; Selby, P.J.; Woods, M.; Barrett, A.; Jameson, B.; Sloane, J.; Lawler, S.D.; Kay, H.E.M.; Lawson, D.; McElwain, T.J. and Alexander, P.: Cyclosporin A to prevent graft versus host disease in man after allogeneic bone marrow transplantation. Lancet 1: 327 (1980).
Powles, R.L. and Morgenstern, G.R.: Cyclosporin A for matched and mismatched bone marrow transplantation in man. Transplantation and Clinical Immunology XIII, p.41 (Excerpta Medica, 1982).
Reitz, B.A.; Bieber, C.P.; Raney, A.A.; Pennock, J.L.; Jamieson, S.W.; Oyer, P.E. and Stinson, E.B.: Orthotopic heart and combined heart and lung transplantation with Cyclosporin A immunosuppression. Transplantation Proceedings XIII: 393–396 (1981).
Ruegger, A.; Kuhn, M.; Lichti, H.; Loosli, H.R.; Huguenin, R.; Quiquerez, C. and von Wartburg, A.: Cyclosporin A, a peptide metabolite from Trichoderma polysporum rifai with remarkable immunosuppressive properties. Helvetica Chimica Acta 59: 1075 (1976).
Starzl, T.E.; Klintmalm, G.B.G.; Porter, K.A.; Iwatsuki, S. and Schröter, G.P.J.: Liver transplantation with use of cyclosporin A and prednisone. New England Journal of Medicine 305: 266 (1981).
Starzl, T.E.; Marchioro, R.L. and Waddell, W.R.: The reversal of rejection in human renal homografts. Surgery, Gynecology and Obstetrics 117: 385 (1963).
Starzl, T.E.; Weil III, R.; Iwatsuki, S.; Klintmalm, G.; Schröter, G.P.J.; Koep, L.J.; Iwaki, Y.; Terasaki, P.I. and Porter, K.A.: The use of Cyclosporin A and Prednisone in cadaver kidney transplantation. Surgery, Gynecology and Obstetrics 151: 17–26 (1980).
Sweny, P.; Crawford, D.; Janossy, G.; Thomas, J.A.; Fernando, O.W. and Moorhead, J.F.: Virus infections, T cell sub-populations and lymphoma in cyclosporin A treated renal allograft recipients. Presented to the British Transplantation Society, November 1980.
Thiru, S.; Calne, R.Y. and Nagington, J.: Lymphoma in renal allograft patients treated with cyclosporin A as one of the immunosuppressive agents. Transplantation Proceedings 13: 359 (1981).
Thomas, H.C.; Routhier, G.; Epstein, O.; Goldstein, G.; Janossy, G. and Sherlock, S.: Cyclosporin A in primary biliary cirrhosis. Gastroenterology 79: 1059 (1980).
Weisinger, D. and Borel, J.F.: Studies on the mechanism of action of cyclosporin A. Zietschrift für Immuniteaetsforsch Immunobiology 156: 454 (1979).
White, D.J.G.; Plumb, A. and Calne, R.Y.: The immune status of transplant recipients immunosuppressed with cyclosporin A. Transplantation Proceedings XIII (No. 3): 1666–1668 (1981).
White, D.J.G.; Plumb, A.M.; Pawelec, G. and Brons, G.: Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells. Transplantation 27: 55 (1979).
White, D.J.G.; Rolles, K. and Ottawa, T.: Cyclosporin A induced long term survival of fully incompatible skin and heart grafts in rats. Transplantation Proceedings 12: 261 (1980).
White, D.J.G.; Timmerman, W. and Davies, H.F.S.: Properties of cyclosporin A induced graft acceptance. Transplantation Proceedings XIII: 379 (1982).
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White, D.J.G. Cyclosporin A. Drugs 24, 322–334 (1982). https://doi.org/10.2165/00003495-198224040-00004
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DOI: https://doi.org/10.2165/00003495-198224040-00004