Tropomyosin-induced arthritis in rats.

Immunization of rats with alpha-tropomyosin (TPM) led to arthritis, uveitis and dermatitis, typical features of Behçet's disease (BD). The present study characterizes the arthritic features of this animal model, not previously described.Lewis rats were immunized with bovine alpha-TPM and another group of rats was treated with neutralizing anti- tumor necrosis factor-alpha (TNF-alpha) antibodies.Clinically more than 90% of the immunized rats developed severe acute arthritis 12 days after vaccination. Rats that were followed-up for 6 months had persistent inflammation of the leg joints. Histologic studies demonstrated predominant mononuclear infiltrations in the acute phase of arthritis; the chronic arthritic process resulted in cartilage and bone damage and abundant fibrosis which led to joint deformations. Male and female rats had a similar clinical course. Analysis of the splenocyte cytokine profile kinetics revealed a persistently high level of interferon-gamma (INF-gamma) and an increase in TNF-alpha secretion during the acute phase. Increasing levels of interleukin (IL)-10 heralded the decline in clinical arthritis. No IL-4 was detected. No arthritis was detected in the rats treated with anti-TNF-alpha antibodies.The data indicates that alpha-TPM serves as an autoantigen to induce acute and chronic destructive arthritis in rats. This model is a TNF-alpha dependent autoimmune disease, with a Th1 cytokine profile.