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D. Sun, Y. Cui, Y. Ke, H. J. Kaplan, H. Shao; Administration of IL-17 to Lewis Rats Inhibited, Rather Than Promoted, the Development of Experimental Autoimmune Uveitis (EAU). Invest. Ophthalmol. Vis. Sci. 2009;50(13):822.
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We have determined whether administration to rats with exogenous IL-17 exacerbates o promotes the EAU development.
Uveitis was induced in Lewis rats either by immunization with 1177-1191 peptide (R16) of interphotoreceptor retinoid-binding protein (IRBP). or adoptive transfer of R16 specific T cells. Then the rats received two i.p. injections of human recombinant IL-17 (hIL-17) on days 4 and 7 after R16 immunization (day 0) or on days 0 and 3 post T cell transfer, while control rats received PBS.
The IL-17-treated animals showed significant amelioration, rather than exacerbation, of disease; in addition, both intensity of the autoreactive response and cytokine production by the autoreactive T cells were significantly decreased. In a chronic relapsing rat EAU model, the IL-17-treated rats developed much milder relapses. In vitro study showed that when IL -17 inhibited the activation of IFN-γ+ R16-specific T cells in a dose-dependent manner, but did not significantly affect the activation of Th17 cells. In addition, recipient rats that received T cells from IL-17-treated, R16-immunized rats developed much weaker disease with a delayed onset compared to those that received T cells from untreated rats. A similar effect of IL-17 was also observed in B10RIII EAU model.
Our results show that IL-17 has anti-inflammatory activity and that this cytokine can suppress the development of autoimmune disease. Both pro- and anti-inflammatory activities of IL-17 require a more thorough investigation of the biological function of IL-17 before targeting this cytokine in therapeutic trials. Supported in part by NIH grants EY014366, EY017373, EY12974, EY14599 and R24 EY015636 as well as an unrestricted grant from Research to Prevent Blindness (RPB), Inc., New York, NY. DS is a recipient of a senior investigator award from RPB. HS is a recipient of a career development award from RPB.
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