Regulatory effects of IFN-β on the development of experimental autoimmune uveoretinitis in B10RIII mice.

BACKGROUND

Experimental 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 FINDINGS: B10RIII 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 IRBP(161-180) on day 13 and control mice were activated with anti-CD3/anti-CD28 antibodies or IRBP(161-180) 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 IRBP(161-180). 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/SIGNIFICANCE: IFN-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.