This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (7)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Uveitis  • Alert me on articles by topic  Social Bookmarking   What's this?

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).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Efficacy of the IL-1 receptor antagonist, anakinra, for the treatment of diffuse anterior scleritis in rheumatoid arthritis. Report of two cases
Botsios et al.
Rheumatology (Oxford) 2007;46:1042-1043.
FULL TEXT  

Essential Role of the MyD88 Pathway, but Nonessential Roles of TLRs 2, 4, and 9, in the Adjuvant Effect Promoting Th1-Mediated Autoimmunity
Su et al.
J. Immunol. 2005;175:6303-6310.
ABSTRACT | FULL TEXT