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RAPID COMMUNICATION
A Metalloproteinase Inhibitor Prevents Lethal Acute Graft-Versus-Host Disease in Mice
Koichi Hattori,
Takao Hirano,
Chifuyu Ushiyama,
Hiroaki Miyajima,
Norifumi Yamakawa,
Tomohiko Ebata,
Yukihisa Wada,
Shoji Ikeda,
Kohichiro Yoshino,
Masatoshi Tateno,
Kazuo Oshimi,
Nobuhiko Kayagaki,
Hideo Yagita, and
Ko Okumura
From the Division of Hematology and the Division of Rheumatology, the Department of Internal Medicine, the Division of Pathobiology, and the Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; the New Drug Discovery Research Laboratory, Kanebo Ltd, Osaka, Japan; and the Department of Pathology, Sapporo City General Hospital, Sapporo, Japan.
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 examined here the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF- and FasL release in a lethal acute GVHD model in mice. Administration of KB-R7785 into (BALB/c × C57BL/6) F1 that received C57BL/6 spleen cells markedly reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The ameliorating effect of KB-R7785 was superior to that of anti-TNF- antibody. Our results suggest that KB-R7785 could be a potent therapeutic agent for GVHD.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 542-548
© 1997 by The American Society of Hematology.
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