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Suppression of Immune-Mediated Ocular Inflammation in Mice by Interleukin 1 Receptor Antagonist Administration
Wee-Kiak Lim, MD;
Chiaki Fujimoto, MD, PhD;
Roxana Ursea, MD;
Sankaranarayana Pillai Mahesh, MD;
Phyllis Silver, BA;
Chi-Chao Chan, MD;
Igal Gery, PhD;
Robert B. Nussenblatt, MD
Arch Ophthalmol. 2005;123:957-963.
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.
Author Affiliations: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Md (Drs Lim, Fujimoto, Ursea, Mahesh, Chan, Gery, and Nussenblatt and Ms Silver); Singapore National Eye Centre and Singapore Eye Research Institute, Singapore (Dr Lim).
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