Collagen-induced arthritis as an animal model for rheumatoid arthritis: focus on interferon-γ.

Rheumatoid arthritis (RA), an autoimmune disease causing inflammation, destruction, and deformity of the joints, affects around 1% of the world population. It is a systemic disease as patients exhibit extra-articular manifestations as well. Collagen-induced arthritis (CIA) in DBA/1 mice is one of the many animal models used to study possible pathogenic mechanisms of RA. It involves immunizing mice with collagen type II in complete Freund's adjuvant. Here we briefly review the general characteristics of RA and CIA and present an overview of data obtained by studying CIA in several gene knockout mice. In particular, detailed analysis of CIA in interferon-gamma (IFN-γ) receptor-deficient mice has pin-pointed IFN-γ as an important cytokine in the pathogenesis and has exposed new functions of IFN-γ in immunological processes. Pilot trials with exogenous IFN-γ in RA have been indicative of a beneficial effect. That improvement of the disease symptoms by IFN-γ treatment was not spectacular may be explained by the fact that RA is a heterogeneous disease in which the severity of the autoimmune disease is strongly determined by environmental factors.