Therapeutic effect of anti-vascular endothelial growth factor receptor I antibody in the established collagen-induced arthritis mouse model.

Abstract

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.