Wang Yi-Ni, Feng Cui-Cui, Liu Jin-Li, Li Fang, Fu Li, Wang Zhao
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Oct;16(5):1135-9.
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 subcutaneously 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.
本研究旨在探讨转化生长因子β(TGF-β)对异基因骨髓移植(allo-BMT)后急性移植物抗宿主病(aGVHD)的影响及机制。受体为雄性BABL/c小鼠,供体为雄性C57BL/6小鼠。通过allo-BMT联合供体来源的T细胞建立aGVHD小鼠模型。实验分为四组:对照组、辐射对照组、移植对照组和TGF-β治疗组。TGF-β治疗组小鼠在移植前两天至移植后七天每天皮下注射TGF-β1(1微克/千克)。结果显示,TGF-β治疗组小鼠的存活时间显著长于移植对照组,且TGF-β治疗组的aGVHD病理变化比移植对照组轻。移植后七天,TGF-β治疗组的IL-2水平显著高于对照组,但显著低于移植对照组。TGF-β治疗组的IL-10水平显著高于移植对照组,但移植对照组的IL-10水平显著低于其他组。结论是,TGF-β可能减轻或抑制致死性aGVHD,并提高小鼠模型allo-BMT后的生存率。调节Th1和Th2细胞因子水平可能是TGF-β预防致死性aGVHD的机制。