Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist.
OBJECTIVE
To determine the effect of overexpression or deletion of interleukin-1 receptor antagonist (IL-1Ra) in collagen-induced arthritis (CIA).


METHODS
Mice overexpressing the IL-1Ra gene under the control of its endogenous promoter, mice lacking IL-1Ra, and normal littermate controls were immunized with bovine type II collagen (CII) and compared in terms of features of CIA.


RESULTS
Mice overexpressing IL-1Ra had a significant reduction in the incidence and severity of CIA. After CII immunization, IL-1Ra messenger RNA was overexpressed in the spleens, but not in the paws, of transgenic mice. Minimal differences were observed in the humoral or cellular immune responses to CII. Mice lacking IL-1Ra had a significantly earlier onset of CIA, with increased severity.


CONCLUSIONS
Endogenous expression of IL-1Ra is a critical determinant of susceptibility to CIA. These findings suggest potential therapeutic interventions for autoimmune arthritis.
Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
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Thornton
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Boivin
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Hirsh
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Hirsch
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Hirsch
D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003094:Collagen / Q000008:administration & dosage / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007111:Immunity, Cellular; D007114:Immunization; D053590:Interleukin 1 Receptor Antagonist Protein; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D003094:Collagen