Reduced incidence and severity of collagen‐induced arthritis in interleukin‐12‐deficient mice

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Abstract
Collagen‐induced arthritis (CIA) is an animal model for rheumatoid arthritis. The disease is elicited by immunization of genetically susceptible DBA/1 mice with type II collagen, resulting in a debilitating arthritis characterized by inflammation and involvement of multiple joints. We investigated the role of endogenous interleukin (IL)‐12 in the pathogenesis of this disease by undertaking an analysis of IL‐12‐deficient mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significantly reduced in mice unable to produce biologically active IL‐12. Concomitant decreases were observed in serum levels of pathogenic, collagen‐specific IgG2a antibodies and collagen‐induced secretion of interferon‐γ 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 required for disease development.