Regulatory Effects of IFN-β on the Development of Experimental Autoimmune Uveoretinitis in B10RIII Mice

Abstract

BackgroundExperimental autoimmune uveoretinitis (EAU) serves as a model for human intraocular inflammation. IFN-β has been used in the treatment of certain autoimmune diseases. Earlier studies showed that it ameliorated EAU; however, the mechanisms involved in this inhibition are still largely unknown.Methodology/Principal FindingsB10RIII mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 161–180 in Complete Freund's adjuvant. Splenocytes from different time points after immunization were used to evaluate the expression of IFN-β. An increased expression of IFN-β was observed during EAU and its highest expression was observed on day 16, 3 days after the peak of intraocular inflammation. Splenocytes and draining lymph node cells from mice immunized with IRBP161-180 on day 13 and control mice were activated with anti-CD3/anti-CD28 antibodies or IRBP161-180 to evaluate the production of IFN-γ and IL-17. The results showed that IFN-γ and IL-17 were significantly higher in immunized mice as compared to the control mice when exposed to anti-CD3/anti-CD28 antibodies. However, the production of IFN-γ and IL-17 was detected only in immunized mice, but not in the control mice when stimulated with IRBP161-180. Multiple subcutaneous injections of IFN-β significantly inhibited EAU activity in association with a down-regulated expression of IFN-γ, IL-17 and an enhanced IL-10 production. In an in vitro system using cells from mice, IFN-β suppressed IFN-γ production by CD4+CD62L− T cells, IL-17 production by CD4+CD62L+/- T cells and proliferation of CD4+CD62L+/- T cells. IFN-β inhibited the secretion of IL-6, but promoted the secretion of IL-10 by monocytes. IFN-β-treated monocytes inhibited IL-17 secretion by CD4+CD62L+/- T cells, but did not influence IFN-γ expression and T cell proliferation.Conclusions/SignificanceIFN-β may exert its inhibitory effect on EAU by inhibiting Th1, Th17 cells and modulating relevant cytokines. IFN-β may provide a potential treatment for diseases mediated by Th1 and Th17 cells.

The comparison of the effects of etanercept, cyclosporine A and triamcinolon acetonide on Th17 in experimental autoimmune uveitis

“…Inflammatory response to concanavalin a is clinically characterized with cells in anterior chamber and vitreous, formation of posterior synechia, and complicated cataract. These characteristics are very similar to those of human uveitis [23,24].…”

“…Experimental autoimmune uveitis has been developed by injecting concanavalin a, retinal S antigen, rhodopsin, recoverin, and interphotoreceptorbinding protein (IRBP) in various experimental studies [22][23][24]. In the present study, we preferred concanavalin a for the induction of the uveitis because of its easy availability.…”

“…Concanavalin a is a non-specific inflammatory agent of the lectin group. It has the mitogenic effect on T cells and some B cells [23,24]. It causes a longlasting inflammatory response including the periods of aggravation and alleviation.…”

“…TNF is a local paracrine and autocrine regulator cytokine for inflammatory cells. TNF-α stimulates mononuclear phagocytes as well as other cell types that produce IL-1, IL-6 and chemokines, and induces the migration of PMN leukocytes [24,26,27]. The animal models has been demonstrated that the number of T-helper type 17 cell (Th17) increased in active uveitis and scleritis while it reduced after treatment.…”

Decreased Expression of the Aryl Hydrocarbon Receptor in Ocular Behcet’s Disease

“…It is classified as an example of an autoinflammatory disorder with marked involvement of both Th1 and Th17 lymphocyte subsets [4–7]. Consistently, strategies aimed at suppressing the abnormal Th1 and Th17 cell response have been reported as a therapeutic approach in BD patients, which is supported by findings in experimental autoimmune uveitis (EAU) models in mice [8, 9]. …”