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Jingtai Cao, Thomas MacPherson, George Yancopoulos, Stanley Wiegand; Pharmacological blockade of interleukin 6 receptor (IL-6R) inhibits the development of ocular inflammation in the murine model of experimental autoimmune uveitis (EAU). Invest. Ophthalmol. Vis. Sci. 2013;54(15):5193.
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To evaluate the effects of systemic administration of a mouse monoclonal antibody against murine IL-6R on ocular inflammation in a murine model of EAU.
EAU was induced by immunization with interphotoreceptor retinoid binding protein (IRBP) in male C57BL/6 mice. In Study 1, a monoclonal murine IL-6R antibody was administered IP at 25 mg/kg or 100 mg/kg on days 5, 7, 9, 11, 14, and 17 after EAU induction. Control animals in which EAU was induced were either untreated, or injected with a control protein (the Fc domain of murine IgG2, 33 mg/kg) following the same treatment schedule. The extent of vitreal and retinal inflammation was assessed in-life by optical coherence tomography (OCT) before IRBP injection (on day-1) and on days 7, 14 and 20 after immunization, and eyes were collected for histological analysis on day 21. A second study was conducted to confirm and extend the results of the first experiment. In Study 2, groups of mice were given one of 3 doses of anti-IL-6R (10 mg/kg, 35 mg/kg or 100 mg/kg IP), or mFc (33 mg/kg IP), every third day from day 5 post EAU induction through day 17.
In Study 1, administration of anti-IL-6R resulted in a dose-related inhibition of uveitis as evidenced by reductions in retinal thickness, morphological abnormalities and inflammatory cell infiltration, as determined by both OCT measures and histological scores (p <0.0003, Kruskal-Wallis Test). Study 2 confirmed that systemic administration of anti-IL-6R resulted in a dose-dependent reduction in vitreoretinal inflammation as determined by OCT, compared to untreated mice, or mice treated with the control protein.
Treatment with an anti-IL-6R mAb starting 5 days post immunization produced a dose-related reduction in inflammation and retinal damage. These results indicate that pharmacological inhibition of IL-6 signaling may have utility in the treatment of inflammatory diseases affecting the retina and uvea track, particularly autoimmune forms of uveitis.
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