Immunosuppressive agents in transplantation: Mechanisms of action and current anti-rejection strategies

Over the past century, the concept of interfering with the immune response at various sites by blocking the formation, stimulation, proliferation, and differentiation of lymphocytes has led to relentless development of new im munosuppressive drugs. These agents are associated with reduced risk of sho rt- and long-term toxicity and have dramatically improved allograft and pat ient survival, especially in recipients of solid organ transplants. Current protocols in such patients are nearly all calcineurin-inhibitor based, usi ng cyclosporine or tacrolimus, as part of dual, triple, or sequential thera py. This review focuses on agents currently in clinical use at transplant c enters in United States. The drugs are described in terms of their basic me chanisms of action, therapeutic uses, clinical studies, and adverse effects . In addition. the efficacy and toxicity of a few promising new therapeutic approaches are examined. Finally, important challenges regarding pharmacol ogical immunosuppression as it relates to solid organ and composite tissue allotransplantation are discussed, (C) 2000 Wiley-Liss, Inc.