Suppression of immune-mediated ocular inflammation in mice by interleukin 1 receptor antagonist administration.

OBJECTIVE To evaluate the effects of an interleukin 1 receptor antagonist (IL-1RA) on the development of immune-mediated ocular inflammation in mice. METHODS Recombinant, human, nonglycosylated IL-1RA (anakinra [kineret]) was tested for its inhibitory effects in 2 systems: (1) experimental autoimmune uveitis induced by interphotoreceptor retinoid-binding protein in B10.A mice using routine procedures and evaluated by clinical and histological examination, and (2) ocular inflammation in mice induced by transfer of hen egg lysozyme-specific T cells to hen egg lysozyme-transgenic mice. Treatment with IL-1RA included daily subcutaneous injections of the drug, at 300 and 500 mg/kg, or phosphate-buffered saline as control. RESULTS Mean +/- SE experimental autoimmune uveitis scores of histological ocular changes of the mice at day 14 postimmunization with interphotoreceptor retinoid-binding protein were 1.5 +/- 0.3 in control mice; 1.0 +/- 0.4 in 300-mg/kg anakinra-treated mice; and 0.5 +/- 0.2 in 500- mg/kg anakinra-treated mice (P = .004). There was a corresponding decrease in the cellular immune response and cytokine production of immune cells in treated mice. Suppression of ocular inflammation by anakinra in the transfer system was also observed (P = .04). CONCLUSION Human IL-1RA suppresses immune-mediated ocular inflammation in mice, affecting both the afferent and efferent components of the pathogenic immune response.Clinical Relevance Systemic administration of IL-1RA may have clinical application in the management of patients with uveitis.