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W. Lim, P.S. Mahesh, C. Fujimoto, I. Gery, C.–C. Chan, Z.–Q. Li, R.B. Nussenblatt; Intravitreal Injection of Interleukin 1 Receptor Antagonist Suppresses Experimental Autoimmune Uveoretinitis in Lewis Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):994.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Proinflammatory cytokines such as IL–1 and TNF–alpha have been implicated to mediate autoimmune diseases including uveitis. We evaluated the effects of intravitreal treatment with an IL–1 receptor antagonist (recombinant nonglycosylated human IL–1 receptor antagonist [rhu IL–1Ra] on the clinical course of EAU in Lewis rats. Methods: Two groups of Lewis rats (9 rats per group) received 3 µl of intravitreal injections of rhu IL–1Ra (7mg/ml) or buffered saline (control) at day 7 post–immunization with IRBP. The eyes were harvested at day 10 post–immunization. Histological scores of disease and intravitreal cytokines levels were evaluated. Another group of Lewis rats (8 rats) received 3ul of intravitreal injections of rhu IL–1 Ra (7mg/ml). These rats were sacrificed at 12 hr intervals and levels of intravitreal rhu IL–1Ra were evaluated. Results: The rats receiving intravitreal rhu IL–1Ra injections had lower mean histologic scores (p=0.006) in the anterior segment, posterior segment and combined (1.17+/– 0.3SE , 0.46+/– 0.18 and 0.81+/– 0.2 respectively) compared with controls (histologic score, anterior segment 2.42,+/–0.6SE, posterior segment 1.25+/–0.46, combined 1.83+/–0.5) at day 10 post–immunization.. The group treated with IL–1Ra had lower cytokines levels in the vitreous; specifically MCP–1, IL–1a, IL–1b IL–2, TNF–alpha, IFN–gamma, MIP2, MIP3, Fractalkine. The half life of intravitreal rhu IL–1Ra was 1 hr. Conclusions: Intravitreal treatment with rhu IL–1Ra at day 7 post immunization with IRBP appeared to reduce the severity of the disease in this initial study. Repeat treatments maybe needed because of the short half–life. These preliminary data suggest intravitreal delivery of IL–1Ra may have clinical application in uveitis.
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