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 in terleukin-l 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 littermat e controls were immunized with bovine type II collagen (CII) and compa red in terms of features of CIA.Results. Mice overexpressing IL-1Ra ha d a significant reduction in the incidence and severity of CIA, After CII immunization, IL-1Ra messenger RNA was overexpressed in the spleen s, but not in the paws, of transgenic mice. Minimal differences,were o bserved in the humoral or cellular immune responses to CII, Mice lacki ng IL-1Ra had a significantly earlier onset of CW,,vith increased seve rity. Conclusion. Endogenous expression of IL-1Ra is a critical determ inant of susceptibility to CLA. These findings suggest potential thera peutic interventions for autoimmune arthritis.