Effects Of Interleukin 1 Receptor Antagonist On Experimental Autoimmune Uveoretinitis In Mice

Abstract

Abstract: : Purpose:The proinflammatory cytokine interleukin 1 (IL–1) has been implicated in mediation of autoimmune diseases including uveitis. Here, we evaluated the role of IL–1 in experimental autoimmune uveitis (EAU), by examining the effects of treatment with an IL–1 receptor antagonist (IL–1Ra) on the development of this disease. Methods:Recombinant human nonglycosylated IL–1Ra ("Anakinra", Amgen) was tested for inhibitory effects in two systems: (1) the conventional IL–1 murine thymocyte proliferation assay, using recombinant murine IL–1 for stimulation, and (2) EAU inducted by IRBP in B10.A mice, using routine procedures. Treatment with IL–1Ra included daily s.c. injections of the drug, at 300mg/kg, or PBS as control. Results: The human IL–1Ra inhibited the murine IL–1 activity in vitro at concentrations as low as10ng/ml. Mean scores of clinical ocular changes of the mice on day 13 post immunization were 1.85±0.8 (mean±SE) in control mice and 0.58±0.1 in treated mice . At day 15 post immunization, the mean clinical scores were 1.95±0.7 (mean±SE) in control mice and 1.35±0.6 in treated mice. Histological scores of eyes collected on day 15 post immunization were: 1.55±0.5 (mean±SE) in controls and 1.0±0.4 in treatment group. Conclusions:Human IL–1Ra inhibits murine IL–1 activity in vitro and suppresses EAU development in mice in vivo. These data indicate that IL–1 plays a role in the pathogenic processes of EAU and, possibly, in human uveitis as well. Testing higher doses of the IL–1Ra in mice and initial studies in humans are under way.

Keywords: autoimmune disease • inflammation • cytokines/chemokines