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).


CONCLUSIONS
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.
Lim
Wee-Kiak
WK
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fujimoto
Chiaki
C
Ursea
Roxana
R
Mahesh
Sankaranarayana Pillai
SP
Silver
Phyllis
P
Chan
Chi-Chao
CC
Gery
Igal
I
Nussenblatt
Robert B
RB
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology / Q000633:toxicity; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D007279:Injections, Subcutaneous; D053590:Interleukin 1 Receptor Antagonist Protein; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000633:toxicity; D012795:Sialoglycoproteins / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D016207:Cytokines; D005136:Eye Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D009113:Muramidase; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D012795:Sialoglycoproteins; D000099214:Retinol-Binding Proteins, Interstitial; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; C421864:hen egg lysozyme