title: Regulatory effects of IFN-β on the development of experimental autoimmune uveoretinitis in B10RIII mice.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
authors.forename: Liping
authors.initials: L
authors.lastname: Du
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D016899:Interferon-beta / Q000378:metabolism* / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012173:Retinitis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014605:Uveitis / Q000150:complications* / Q000276:immunology / Q000473:pathology
chemical_list: D007378:Interleukins; D016899:Interferon-beta; D007371:Interferon-gamma