Cyclosporine.

Abstract

Cyclosporine is more selective in its suppression of the immune system than previously available drugs. Although the exact mechanism of action is not yet known, it probably acts by interfering with lymphokine secretion. It primarily inhibits T-lymphocyte responses, although some B cell responses are also affected. Neutrophils and platelet formation are spared. Its efficacy in prolonging the survival of transplanted organs in experimental animals has been a stimulus to the study of graft-host interactions and to the growth of clinical transplantation. In clinical renal transplantations, many, but not all, centers have observed an improvement in graft survival. Nephrotoxicity is common--the average creatinine level of a stable patient on cyclosporine is typically a third again higher than in a patient on conventional therapy. Results of studies up to three years have not shown a further deterioration in renal function, but longer term data are unavailable. Because patients on cyclosporine often have less severe rejection and require lower dosages of corticosteroids, progress in cardiac and hepatic transplantation is being made. The role of blood level monitoring in the avoidance of nephrotoxicity and other side effects remains unsettled. Only further experience with measuring concentrations of the drug in the blood will reveal if it is useful. Numerous drug interactions are important, particularly with aminoglycosides and amphotericin.