The antigen induced arthritis model: the relevance of the method of induction to its use as a model of human disease.

The much favoured ovalbumin antigen induced model of arthritis in rabbits is widely used in rheumatoid arthritis (RA) research. When examined histologically, it was found to have important deficiencies as parallels to the human disease. After sensitization to ovalbumin, 2 intraarticular challenge doses of a magnitude at each end of the spectrum used by investigators were used in 152 rabbits. The effects of the high and low dose challenges were examined histologically with particular attention to the articular cartilage. With high doses, the gross and histological changes in the knee joint were remarkably akin to acute cartilage necrosis rather than RA1. In the low dose, a milder smoldering arthritis was produced. These observations suggest that, depending on the challenge dose used, there is a tremendous variability in the kind of arthritis produced by the antigen induced arthritis model. Furthermore, it is suggested that previous conclusions about the pathophysiology and immunology of RA drawn from the models that produce a rapid and severe arthritis should be reexamined.