Open AccessAltered susceptibility to collagen‐induced arthritis in transgenic mice with aberrant expression of interleukin‐1 receptor antagonist
Author(s) -
Ma Yuhe,
Thornton Sherry,
Boivin Gregory P.,
Hirsh David,
Hirsch Raphael,
Hirsch Emmet
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199810)41:10<1798::aid-art11>3.0.co;2-l
Subject(s) - interleukin 1 receptor antagonist , arthritis , collagen induced arthritis , genetically modified mouse , antagonist , transgene , receptor antagonist , interleukin , endocrinology , receptor , medicine , immunology , biology , cytokine , gene , genetics
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. Conclusion Endogenous expression of IL‐1Ra is a critical determinant of susceptibility to CIA. These findings suggest potential therapeutic interventions for autoimmune arthritis.