Differential effects of anti Fas ligand and anti TNF-alpha antibodies on GVHD pathologies

肿瘤坏死因子(TNF)和Fas配体(FasL)参与了移植物抗宿主病(GVHD)的发病过程，移植物抗宿主病是异基因骨髓移植后的主要并发症。我们观察了金属蛋白酶抑制剂(KB-R7785)对小鼠骨髓移植后急性移植物抗宿主病(GVHD)模型中肿瘤坏死因子-α和FasL释放的改善作用。在接受C57BL/6骨髓细胞和脾细胞照射的(BALB/c x C57BL/6)F1小鼠中，注射KB-R7785可降低死亡率和体重减轻，并与肝脏、肠道和造血组织中GVHD病理的轻微征象相关。KB-R7785处理不影响供者细胞的造血重建。因此，KB-R7785有可能成为治疗骨髓移植后移植物抗宿主病的有效药物。

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), that is a major complication after allogeneic bone marrow transplantation. We here examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 into irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The KB-R7785 treatment did not affect the hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.