Markus P M, Cai X, Ming W, Demetris A J, Fung J J, Starzl T E
Department of Surgery, University of Pittsburgh, Pennsylvania 15213.
Transplantation. 1991 Oct;52(4):590-4. doi: 10.1097/00007890-199110000-00002.
FK506 and cyclosporine were used for the prevention of acute graft-versus-host disease. Acute GVHD was induced in Lewis rats by total-body irradiation and subsequent reconstitution with allogeneic (ACI) bone marrow and spleen cells (BMTx). GVHD was assessed by both clinical and histologic parameters during the experiment duration of 60 days, and longer for selected animals. All untreated BM recipients died within 26 days from severe acute GVHD. GVHD was prevented with CsA during the period of immunosuppressive therapy, but it appeared within a few days afterward. FK506-treated BM recipients were also protected, but they had a markedly prolonged GVHD-free period after therapy was discontinued. Most such animals eventually developed GVHD but with notable exceptions. Maintenance therapy with doses of FK506 as low as 0.1 mg/kg every other day (1/20 of daily induction dose) was infallible insurance against delayed GVHD. The relevance of these findings to GVHD caused by lymphoid-containing solid organs such as the intestine was discussed.
FK506和环孢素用于预防急性移植物抗宿主病。通过全身照射以及随后用同种异体（ACI）骨髓和脾细胞进行重建（骨髓移植），在Lewis大鼠中诱导急性移植物抗宿主病。在60天的实验期间，通过临床和组织学参数评估移植物抗宿主病，对于选定的动物评估时间更长。所有未治疗的骨髓移植受体在26天内死于严重的急性移植物抗宿主病。在免疫抑制治疗期间，环孢素可预防移植物抗宿主病，但在治疗后几天内该病又会出现。接受FK506治疗的骨髓移植受体也受到了保护，但在治疗停止后，它们的无移植物抗宿主病期明显延长。大多数此类动物最终会发生移植物抗宿主病，但也有明显的例外情况。每隔一天使用低至0.1mg/kg的FK506剂量进行维持治疗（每日诱导剂量的1/20）是预防延迟性移植物抗宿主病的可靠保障。讨论了这些发现与由含淋巴细胞的实体器官（如肠道）引起的移植物抗宿主病的相关性。
