Collagen-induced arthritis in mice.

Collagen-induced arthritis in mice has been widely used to address questions of disease pathogenesis and to validate therapeutic targets for human rheumatoid arthritis. Arthritis is normally observed about 3 wk after immunization with autologous or heterologous type II collagen in complete Freund's adjuvant and susceptibility to the disease is strongly associated with major histocompatibility complex class II genes. The development of collagen-induced arthritis is associated with strong T- and B-cell responses to type II collagen and the chief pathological features of the disease include a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin--1beta, are abundantly expressed in the arthritic joints of mice with collagen-induced arthritis and, as in human rheumatoid arthritis, blockade of these molecules is effective in reducing the severity of disease.