The role of IL-4 in regulation of murine collagen-induced arthritis.

Collagen-induced arthritis (CIA) is a murine model of autoimmune-mediated polyarthritis. CIA can be prevented by the administration (intravenously) of CII, inducing regulatory CD4+ T cells which produce Th2 cytokines. However, the relative importance of IL-4 in suppressing arthritis remains unclear. To address this question, a neutralizing monoclonal antibody to IL-4 was given to mice treated with tolerized, CII-specific cells. The antibody significantly reversed the expected suppression of arthritis. Moreover, CII administered intravenously to DBA/1 IL4-/- mice (developed by backcrossing C57B1/6 IL4-/- to wild-type DBA/1 mice) was completely ineffective in suppressing disease. These data support the importance of IL-4 in the regulation of autoimmune arthritis. Compensatory increases in mRNA message for other Th2 cytokines were observed, but they did not restore suppression of arthritis. Antibodies to CII, mostly IgG2a, were increased in IL4-/- mice. These studies represent a unique opportunity to analyze the role of IL-4 and its absence on an autoimmune murine model of arthritis.