Berney T, Buhler L H, Majno P, Mentha G, Morel P
Division of Visceral and Transplantation Surgery, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.
Transplant Proc. 2004 Mar;36(2 Suppl):362S-366S. doi: 10.1016/j.transproceed.2003.12.035.
Protocols for islet transplantation have to take into account the diabetogenicity/islet toxicity of the immunosuppressive agents, namely corticosteroids and calcineurin inhibitors, most notably tacrolimus. The development by the Edmonton group of a sirolimus-based, steroid-free, low-tacrolimus regimen was a significant breakthrough that allowed the rate of insulin independence after islet transplantation to increase from 13% to 80% at 1 year. Drawbacks include the side effects of sirolimus and the reduction in insulin independence to 50% at 3 years, the latter being attributed to prolonged tacrolimus exposure. Currently explored alternatives to tacrolimus include cyclosporine, mycophenolate mofetil, and the novel agent FTY 720. Perspectives for the near future involve the achievement of "prope tolerance" by strategies using lymphocyte-depleting antibodies (anti-thymocyte globulin, campath-1H, hOKT3gamma1 [ala,ala]), or costimulatory blockade (anti-CD154 mAbs, CTLA4-Ig).
胰岛移植方案必须考虑免疫抑制剂（即皮质类固醇和钙调神经磷酸酶抑制剂，尤其是他克莫司）的致糖尿病性/胰岛毒性。埃德蒙顿研究小组开发的基于西罗莫司、无类固醇、低剂量他克莫司的方案是一项重大突破，使胰岛移植后1年胰岛素非依赖率从13%提高到了80%。缺点包括西罗莫司的副作用以及3年后胰岛素非依赖率降至50%，后者归因于长期暴露于他克莫司。目前正在探索的他克莫司替代药物包括环孢素、霉酚酸酯和新型药物FTY 720。近期的展望包括通过使用淋巴细胞清除抗体（抗胸腺细胞球蛋白、campath-1H、hOKT3γ1[ala,ala]）或共刺激阻断（抗CD154单克隆抗体、CTLA4-Ig）的策略实现“前体耐受”。
