(4-(n-hydroxyamino)-2r-isobutyl-3s-methylsuccinyl)-l-phenylglycine-n-methylamide and Weight-Loss

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.

Topics: Animals; Bone Marrow Transplantation; Cell Separation; Female; Flow Cytometry; Glycine; Graft vs Host Disease; Hematopoiesis; Hydroxamic Acids; Lymphocytes; Metalloendopeptidases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Protease Inhibitors; Weight Loss