Wang C, Sun J, Sheil A G, McCaughan G W, Bishop G A
Royal Prince Alfred Hospital, Department of Transplantation, The University of Sydney, New South Wales, Australia.
Transplantation. 2001 Jul 15;72(1):44-51. doi: 10.1097/00007890-200107150-00011.
The effects of immunosuppressive drugs on transplant tolerance have not been extensively studied, although their effect on rejection is well established.
We examined the effects of a short course of treatment with the immunosuppressive drug methylprednisolone (MP) on the survival of PVG liver allografts in Dark Agouti (DA) recipients that accepted the livers and in Lewis recipients that rejected the livers. Infiltration of liver allografts was examined by immunohistochemical staining of liver sections, and apoptosis was measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling.
A 5-day course of MP (days 0 to 4) led to rejection of four of six livers (mean survival time [MST] 99 days) in DA recipients compared with long-term survival (MST >100 days) in untreated animals. Delayed administration of MP (days 3 to 7) exacerbated rejection in DA recipients, and all eight animals rejected the graft (MST 68.5 days). Treatment of Lewis recipients with MP did not significantly prolong survival when administered from days 0 to 4 (MST 13 days), although delay of administration improved the outcome. Treatment from days 3 to 7 resulted in an MST of 21 days, whereas treatment from days 7 to 11 resulted in an MST of 41.5 days. MP treatment from day 3 to day 7 reduced T cells and interleukin 2 receptor-expressing cells but increased the numbers of apoptotic cells infiltrating both DA and Lewis strain allografts.
These results show that immunosuppression with MP inhibits both spontaneous tolerance and rejection of liver allografts in a rat model and question the efficacy of administering MP to all liver allograft recipients from the time of transplantation.
尽管免疫抑制药物对移植排斥的作用已得到充分证实，但其对移植耐受的影响尚未得到广泛研究。
我们研究了免疫抑制药物甲泼尼龙（MP）短期治疗对接受肝脏的暗褐鼠（DA）受体和排斥肝脏的Lewis受体中PVG肝同种异体移植存活的影响。通过肝脏切片的免疫组织化学染色检查肝同种异体移植的浸润情况，并通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法测量细胞凋亡。
与未治疗动物的长期存活（平均存活时间[MST]>100天）相比，DA受体接受5天疗程的MP（第0至4天）导致6个肝脏中的4个发生排斥（MST 99天）。MP延迟给药（第3至7天）加剧了DA受体的排斥反应，所有8只动物均排斥移植肝（MST 68.5天）。从第0至4天对Lewis受体进行MP治疗并不能显著延长存活时间（MST 13天），尽管延迟给药改善了结果。第3至7天的治疗导致MST为21天，而第7至11天的治疗导致MST为41.5天。第3天至第7天的MP治疗减少了T细胞和表达白细胞介素2受体的细胞，但增加了浸润DA和Lewis品系同种异体移植的凋亡细胞数量。
这些结果表明，在大鼠模型中，MP免疫抑制既抑制了肝同种异体移植的自发耐受，也抑制了排斥反应，并对从移植时起对所有肝同种异体移植受体给予MP的疗效提出了质疑。
