Immunosuppression following heart transplantation: Established concepts and new perspectives [Immunsuppression nach herztransplantation: Bewährte konzepte und neue perspektiven]

In the early years of heart transplantation, success of this therapy was limited by the lack of immunosuppressive drugs which could effectively suppress rejection without increasing the risk for life-threatening infection. Only the introduction of cyclosporin A as the basis for a triple immunosuppressive regimen including azathioprin and steroids improved survival after heart transplantation significantly. Since those immunosuppressants were associated with a wide spectrum of adverse events, a search for new agents with equivalent immunosuppressive activity and a reduced array of side effects was initiated. This led to the development of tacrolimus and mycophenolate mofetil as alternatives for cyclosporin A and azathioprin, respectively. Several clinical studies indicated that tacrolimus and mycophenolate mofetil were associated with a greater immunosuppressive potential as compared to cyclosporin A and azathioprin. However, the spectrum of side effects was still not negligible. New perspectives arose with the availability of rapamycin and IL-2-receptor antagonists. The combination of these drugs with the established immunosuppressive drugs resulted in a more sufficient suppression of acute rejection. Their spectrum of side effects and long-term immunosuppressive efficacy, however, have not clearly been identified so far. The ultimate goal of transplantation, however, is the induction of recipient tolerance towards the transplanted organ without the need for lifelong immunosuppression. Animal studies have shown that tolerance is inducible by simultaneous donor-specific bone marrow transplantation and costimulatory blockade of the recipient. Before this concept can be evaluated in the clinic, its test in large animal models is required. © Steinkopff Verlag 2002.