Inhibition of very late antigen-4 and leukocyte function-associated antigen-1 in experimental autoimmune uveoretinitis

实验性自身免疫性葡萄膜视网膜炎中极晚期抗原 4 和白细胞功能相关抗原 1 的抑制

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作者:Waka Ishida, Yosuke Harada, Ken Fukuda, Osamu Taguchi, Hideo Yagita, Atsuki Fukushima

Abstract

B10.RIII mice were immunized with interphotoreceptor retinoid binding protein peptide to induce uveitis. Mice were injected intraperitoneally with anti-very late antigen-4 (VLA-4), anti-leukocyte function-associated antigen-1 (LFA-1), or a control Ab every other day from Day 5 to Day 13 post-immunization. The eyes and spleens were harvested on Day 14 or 28. The eyes were used for histologic/cytokine mRNA expression analyses. The spleens were used for Ag-recall cytokine production assays and intracellular cytokine assays. Treatment with both Abs led to a profoundly significant reduction in severity of uveitis and cytokine mRNA expression in the eye. However, cytokine production by splenocytes was significantly upregulated. Discontinuation of Ab treatment led to an increase in uveitis severity and cytokine mRNA expression in the eye, but led to a decrease in cytokine production and intracellular IFN-γ(+) and IL-17A(+)cytokine profile by splenocytes. Thus, blockade of these molecules using specific Abs may be a therapeutic option for patients with uveitis; however, such treatment must be continued.

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