Oral administration of interferon-β suppresses experimental autoimmune uveoretinitis

Suzuki, Jun; Sakai, Jun‐ichi; Okada, Annabelle A.; Takada, Eiko; Usui, Masahiko; Mizuguchi, Junichiro

doi:10.1007/s00417-001-0425-z

Cited by 14 publications

(12 citation statements)

References 39 publications

(45 reference statements)

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“…On the other hand, it promoted the secretion of IL-10. Our data on IFN-γ production are in agreement with earlier studies by Suzuki et al in the EAU model in rats [30]. These results are also consistent with those reported in the treatment of MS patients with IFN-β [2], [7], [36].…”

Section: Discussionsupporting

confidence: 93%

“…However, unexpectedly, we failed to find any influence of in vivo IFN-β treatment on T cell proliferation assays in vitro. This result is in disagreement with the data published by Suzuki et al [30] but generally consistent with that reported by Hedegaard et al [36]. In the latter study, IFN-β treatment of MS patients was not associated with an effect of this protein on T cell proliferation.…”

Section: Discussioncontrasting

confidence: 51%

“…Only few studies have addressed the effect of IFN-β on EAU and mainly concentrated on T cell proliferation and IFN-γ production [30]. We extended these studies and firstly examined whether and how IFN-β was expressed during this model.…”

Section: Discussionmentioning

confidence: 99%

“…IFN-α, which also belongs to the type I interferons, has been used in Europe to treat various forms of uveitis [25]–[27] and EAU [28]–[29]. Earlier studies from Japan have shown that oral IFN-β could ameliorate EAU in rats and evidence was obtained that this was mediated via NK or NKT cells [30]. Whether IFN-β may exert its effect by interfering with Th1 and/or Th17 lineages was not addressed yet and was therefore the subject of the study presented here.…”

Section: Introductionmentioning

confidence: 99%

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

Sun

Yang

et al. 2011

PLoS ONE

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Sun

Yang

et al. 2011

PLoS ONE

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show abstract

“…There is some evidence that NK cells do play a role in animal models of uveitis. [36][37][38] A study in humans with uveitis found increased peripheral blood NK cells of a type called CD56bright when the uveitis improved with IL-2 receptor inhibition. 39 This subset of NK cells produces cytokines and is not cytotoxic, and KIRs do not appear to be expressed in these cells.…”

Section: Resultsmentioning

confidence: 99%