Schulak J A, Monson D, Shelby J, Corry R J
Transplantation. 1983 Sep;36(3):289-93. doi: 10.1097/00007890-198309000-00012.
Cyclosporine was evaluated for its ability to delay or prevent accelerated rejection in a model of the second-set immune response. Lewis rats sensitized by LBN skin grafts or subcutaneous heart fragments experienced accelerated rejection of heterotopic, vascularized LBN hearts with a mean survival time (MST) of approximately 5 days versus MST of 9.5 days for primary grafts. A short course of cyclosporine (10 mg/kg/day for 10 days) significantly prolonged graft survival in presensitized hosts to approximately 12 days (P less than 0.01) as compared with the nontreated controls. Adjunctive splenectomy failed to further extend graft survival; MSTs were 12.0 and 5.7 days with and without cyclosporine, respectively. A comparable abrogation of second-set rejection was also achieved with a short course of antithymocyte serum (MST of 10.6 days). Rejection promptly ensued in all of the above groups shortly after cessation of immunosuppression. In contrast, a maintenance regimen of cyclosporine, given in a tapering dose, markedly extended graft survival to from 77 to 100+ days. Again, however, rejection eventually occurred following withdrawal of the cyclosporine. These data suggest that cyclosporine can indeed effectively prolong allograft survival in presensitized hosts.
在二次免疫反应模型中,对环孢素延缓或预防加速性排斥反应的能力进行了评估。通过LBN皮肤移植或皮下心脏碎片致敏的Lewis大鼠,对异位血管化LBN心脏出现加速性排斥反应,平均存活时间(MST)约为5天,而初次移植的MST为9.5天。与未治疗的对照组相比,短疗程的环孢素(10 mg/kg/天,共10天)可使预致敏宿主的移植物存活时间显著延长至约12天(P<0.01)。辅助性脾切除术未能进一步延长移植物存活时间;使用环孢素和未使用环孢素时的MST分别为12.0天和5.7天。短疗程的抗胸腺细胞血清也能达到类似的消除二次排斥反应的效果(MST为10.6天)。在上述所有组中,免疫抑制停止后不久即迅速发生排斥反应。相比之下,以逐渐减量的方式给予环孢素维持治疗方案,可使移植物存活时间显著延长至77至100多天。然而,再次出现的情况是,停用环孢素后最终仍发生了排斥反应。这些数据表明,环孢素确实能够有效延长预致敏宿主同种异体移植物的存活时间。