Hattori K, Hirano T, Ushiyama C, Miyajima H, Yamakawa N, Ikeda S, Yoshino K, Tateno M, Oshimi K, Kayagaki N, Yagita H, Okumura K
Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Bone Marrow Transplant. 1999 Jun;23(12):1283-9. doi: 10.1038/sj.bmt.1701792.
Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 to 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 hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.
肿瘤坏死因子（TNF）和Fas配体（FasL）与移植物抗宿主病（GVHD）的发病机制有关，GVHD是同种异体骨髓移植后的一种主要并发症。我们在小鼠骨髓移植后的急性GVHD模型中研究了一种金属蛋白酶抑制剂（KB-R7785）的改善作用，该抑制剂可抑制TNF-α和FasL的释放。给接受C57BL/6骨髓细胞和脾细胞的经照射的（BALB/c×C57BL/6）F1小鼠施用KB-R7785，可降低死亡率和体重减轻，并伴有肝脏、肠道和造血组织中GVHD病理的轻微迹象。KB-R7785治疗不影响供体细胞的造血重建。因此，KB-R7785可能是骨髓移植后GVHD的一种有效治疗药物。
