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 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.
Hattori
K
K
Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Hirano
T
T
Ushiyama
C
C
Miyajima
H
H
Yamakawa
N
N
Ikeda
S
S
Yoshino
K
K
Tateno
M
M
Oshimi
K
K
Kayagaki
N
N
Yagita
H
H
Okumura
K
K
D000818:Animals; D016026:Bone Marrow Transplantation; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006410:Hematopoiesis / Q000187:drug effects; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
D006877:Hydroxamic Acids; C107086:KB R7785; D011480:Protease Inhibitors; D008666:Metalloendopeptidases; D005998:Glycine