Therapeutic effect of anti-vascular endothelial growth factor receptor I antibody in the established collagen-induced arthritis mouse model.
Synovial angiogenesis plays an important role in the inflammation in rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) is a key molecule in angiogenesis and binds to specific receptors, known as vascular endothelial growth factor receptor I (VEGF RI). In this study, we investigated the therapeutic efficacy of anti-VEGF RI antibody (Ab) on RA using a collagen-induced arthritis (CIA) mouse model. Twelve DBA/1 mice were divided into three groups. All mice except controls were injected with type II collagen. Mice in the anti-VEGF-RI-Ab-treated groups were injected on one posterior paw with 50 microg anti-VEGF RI Ab twice weekly for 3 weeks. Arthritis score and paw thickness were measured and histopathologic assessment of joint sections was performed by hematoxylin-eosin. The infiltration of CD45+ inflammatory cells and neovascularization were evaluated by immunohistochemical staining. Anti-VEGF RI Ab significantly attenuated the arthritis severity and histopathologic findings in the CIA mice model. The infiltration of CD45+ cells decreased in anti-VEGF-RI-Ab-treated joint tissues. Staining for CD31 revealed reduced synovial neovascularization after anti-VEGF RI Ab treatment. The data showing that in vivo administration of anti-VEGF RI Ab suppressed arthritis in established CIA mice suggest anti-VEGF RI Ab treatment may serve as a new therapeutic modality for RA.
Choi
Sang Tae
ST
Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Disease, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Kim
Ji Hye
JH
Seok
Jae-Yeon
JY
Park
Yong-Beom
YB
Lee
Soo-Kon
SK
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D006614:Hindlimb; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D013583:Synovial Membrane / Q000098:blood supply; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D040281:Vascular Endothelial Growth Factor Receptor-1