REDUCED INCIDENCE AND SEVERITY OF COLLAGEN-INDUCED ARTHRITIS IN INTERLEUKIN-32-DEFICIENT MICE

Collagen-induced arthritis (CIA) is an animal model for rheumatoid art hritis. The disease is elicited by immunization of genetically suscept ible DBA/1 mice with type II collagen, resulting in a debilitating art hritis characterized by inflammation and involvement of multiple joint s. We investigated the role of endogenous interleukin (IL)-12 in the p athogenesis of this disease by undertaking an analysis of IL-12-defici ent mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significa ntly reduced in mice unable to produce biologically active IL-12. Conc omitant decreases were observed in serum levels of pathogenic, collage n-specific IgG2a antibodies and collagen-induced secretion of interfer on-gamma by immune splenocytes in vitro, consistent with an impaired T helper-1 response. There were, however, a few animals which developed severe disease in a single paw in spite of this highly diminished Th1 response. Taken together, these results demonstrate an important role for IL-12 in the pathogenesis of CIA, although it is not absolutely r equired for disease development.