Neuhaus P, Klupp J, Langrehr J M
Department of Surgery, Charité Virchow, Berlin, Germany.
Liver Transpl. 2001 Jun;7(6):473-84. doi: 10.1053/jlts.2001.24645.
Inhibitors of the mammalian target of rapamycin are a new class of immunosuppressants. In contrast to other macrolides, such as tacrolimus and cyclosporine A, they do not inhibit calcineurin and thus signal I of T-cell activation. By inhibiting signal III, the mechanism of action and side effects of sirolimus (rapamycin) and its derivative RAD are distinct from other immunosuppressants. Reports of synergism with cyclosporine A and tacrolimus in preclinical and clinical studies, avoidance of nephrotoxicity, and possible treatment or prevention of chronic allograft rejection are leading to high expectations for this new class of immunosuppressants. Furthermore, studies evaluating tolerance induction are being conducted. This review summarizes preclinical and clinical results published to date and exploits the future value of sirolimus and RAD for clinical transplantation.
雷帕霉素哺乳动物靶点抑制剂是一类新型免疫抑制剂。与其他大环内酯类药物（如他克莫司和环孢素A）不同，它们不抑制钙调神经磷酸酶，因此不影响T细胞激活信号I。通过抑制信号III，西罗莫司（雷帕霉素）及其衍生物RAD的作用机制和副作用与其他免疫抑制剂不同。临床前和临床研究中关于与环孢素A和他克莫司协同作用、避免肾毒性以及可能治疗或预防慢性移植物排斥反应的报道，使得人们对这类新型免疫抑制剂寄予厚望。此外，正在进行评估诱导耐受的研究。本综述总结了迄今为止已发表的临床前和临床研究结果，并探讨了西罗莫司和RAD在临床移植中的未来价值。
