TGF-β减轻异基因骨髓移植小鼠急性移植物抗宿主病

为了探讨转化生长因子β（TGF—β）对小鼠异基因骨髓移植后急性移植物抗宿主病发生发展的影响，用C57BL／6小鼠作为供鼠，BABL/c小鼠为受鼠，建立小鼠同种异基因骨髓移植模型。BABL／c受鼠随机分为4组：空白对照组、单纯照射组、移植对照组和TGF—β实验组。TGF—β实验组于移植前2天至移植后7天每日皮下注射TGF—β1（1μg/kg）。结果显示：TGF-β实验组小鼠生存时间明显长于移植对照组（P〈0．01），TGF—β实验组小鼠小肠、皮肤及肝脏GVHD病理改变明显轻于移植对照组。移植后7天TGF—β实验组小鼠血清IL-2浓度较空白对照组高，但远低于移植对照组；TGF—β实验组血清IL—10浓度明显高于移植对照组。结论：TGF—β能够减轻或抑制小鼠allo—BMT后致死性的aGVHD发生，提高移植后存活率。TGF—β可能使Th1细胞向Th2细胞偏移，抑制IL-2等Th1类细胞因子的分泌，同时促进了Th2类细胞因子IL—10的表达，降低aGVHD的发生。

Transforming growth factor beta alleviates acute graft-versus-host-disease after allogeneic bone marrow transplantation in murine model

This study was purposed to investigate the effects and mechanism of transforming growth factor beta (TGF-beta) on acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT). The recipients were male BABL/c mice, while the donors were male C57BL/6 mice. The murine model of aGVHD had been established by allo-BMT with donor derived T cells. Experiment was divided into four groups: control group, radiation control group, transplantation control group and TGF-beta treated group. Mice in TGF-beta treated group were daily subcutaneaesly injected TGF-beta1 (1 microg/kg) in two days before transplantation until seven days after it. The results showed that the survival time of mice in TGF-beta treated group was significantly longer than that in transplantation control group, and the aGVHD pathological changes in TGF-beta treated group were milder than that in transplantation control group. At seven days after transplantation, the level of IL-2 in TGF-beta treated group was significantly higher than that in control group, but significantly lower than that in transplantation control group. The level of IL-10 in TGF-beta treated group was significantly higher than that in transplantation control group, but the level of IL-10 in transplantation control group was significantly lower than that in other groups. It is concluded that TGF-beta may alleviate or suppress lethal aGVHD, and elevate the survival rate after allo-BMT in murine model. Accommodating of the Th1 and Th2 cytokine levels is the possible mechanism of TGF-beta preventing lethal aGVHD.