The use of cyclosporin in organ transplants

Cyclosporin is a metabolite isolated from culture broths of the fungus Tolypocladium inflatum Gams which was shown to be immunosuppressive by Borel et al. in rats, mice and guinea-pigs.1.2 Cyclosporin may directly block the release of interleukin I from activated T helper cells and indirectly block the release of interleukin II from macrophages, thus suppressing both cellular and humoral immunity. The drug is most effective if given at the time of immunization or, antigenic challenge, but the suppressive effect is reversible. These effects are not accompanied by bone marrow depression, and do not lower resistance to bacterial and fungal infections. There is some doubt about the effect of cyclosporin on viral infections. When cyclosporin was first used in patients by Caine et al. 3 in 1978, it was hoped that no other drug would be routinely required. However, most of their experience has been with delayed administration of the drug because of the fear of nephrotoxicity and hepatotoxicity. Azathioprine and prednisone were used initially until renal and hepatic functions were adequate. Then l:yclosporin was begun, and the steroid dose was slowly reduced and withdrawn. 4 The supervention of acute rejection during treatment with azathioprine and prednisone was troublesome. In late 1979, cyc1osporin became available for preliminary testing in the USA. The authors' initial experience in cadaver renal transplantation5 1ed them to believe that the combination of cyclosporin and steroids is a more effective and safe immunosuppressive treatment than cyclosporin alone. From then until the end of 1984, approximately 500 cadaver renal,6 300 hepatic,7 100 cardiac and 10 pancreatic transplants were carried out at the University Health Centre of Pittsburgh under cyclosporin-steroid treatment. The authors' experience is briefly summarized here as an example of the use of cyclosporin.