A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in t he pathogenesis of graft-versus-host disease (GVHD), which is a major compl ication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibi ts TNF-alpha and Fast release in a murine acute GVHD model after bone marro w transplantation. Administration of KB-R7785 to irradiated (BALB/c x C57BL /6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduce d the mortality and weight loss in association with minimal signs of GVHD p athology in the liver, intestine, and hematopoietic tissues, The KB-R7785 t reatment did not affect hematopoietic reconstitution by donor cells, Theref ore, KB-R7785 could de a potent therapeutic agent for GVHD after bone marro w transplantation.