Acceleration of onset of collagen‐induced arthritis by intra‐articular injection of tumour necrosis factor or transforming growth factor‐beta

SUMMARY We examined whether tumour necrosis factor (TNF)or transforming growth factor‐beta 1 (TGF‐β1) could alter the course of collagen‐induced arthritis (CIA). Injection of 100 ng TNF or 500 ng TGF‐β1 into ankle joints of normal rats induced a very limited inflammatory response, observable only upon histological analysis. However, when injected into ankle joints of rats 9 days after immunization with bovine type II collagen (CII), identical doses of TNF or TGF‐β1 induced a sustained, clinically obvious inflammation and oedema that began within 8 h on average, as compared to 90 h in CII‐inimunized control rats given no injections or intra‐arlicular injections of buffer. The incidence of arthritis at 2 weeks post‐immunization was 100% for TNF‐injected hindpaws, compared with 55% for the control groups, a statistically significant difference. In rats passively immunized with a subarthritic dose of affinity purified antibody to rat‐CII, intra‐articular injection of 100 ng TNF or 500ng of TGF‐β1 also induced intense, though transient arthritis. The rapid proinflammatory effects in CIA described in this study and the synergy demonstrated between anti‐CII IgG and either cytokine, suggest that these cytokines can participate locally in the pathogenesis of arthritis.