HISTOLOGICAL, IMMUNOLOGICAL AND BIOCHEMICAL STUDIES ON TYPE II COLLAGEN-INDUCED ARTHRITIS IN RATS

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Abstract
Lewis strain rats were used for induction of arthritis by type II collagen immunization. Among 3 litters of Lewis rats tested, the incidence of arthritis after a single immunization of bovine type II collagen varied from 100 to 10% depending on the litter; established inflammatory reactions lasted over 10 wk in all litters. Microscopic observation of the affected knee joints showed progressive destruction of the articular cartilage and subchondral bone accompanied by marked proliferative synovitis and subsequent replacement of the tissues by extensive fibrous tissue, indicating ankylosis. Immunological studies on arthritic and non-arthritic rats after immunization with collagen showed that humoral and cellular immune responses to type II collagen were statistically correlated to each other and significantly higher in arthritic rats than in non-arthritic rats. The serum antibody titer to rat type II collagen was increased in parallel with that to bovine type II collagen, suggesting that immune reactions to autologous type II collagen may be involved in the development of arthritis. In synovial fluids accumulated in the inflamed knee joints, a measurable amount of collagenase was detected. Arthritic synovial cells produced more collagenase than normal cells (P < 0.01). The pathophysiological process of collagen-induced arthritis in rat resembles that of rheumatoid arthritis. This system will be a suitable experimental model for the elucidation of destructive process of the articular tissue in rheumatoid arthritis.