PROGRESSION OF ARTICULAR DESTRUCTION AND THE PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN ANTIGEN-INDUCED ARTHRITIS IN RABBITS

We examined the progression of articular destruction and the productio n of tumour necrosis factor-alpha (TNF-alpha) in antigen-induced arthr itis (AIA) in rabbits, i.e. flare-ups of inflammation induced by repea ted intra-articular injections (single, twice and three times) of anti gen. A marked progression of articular destruction and an infiltration of inflammatory cells in the synovium were observed with the increase in the number of antigen injections. An immunohistochemical analysis of the synovial lesions following three injections of antigen revealed that the lymphoid follicles consisted mainly of CD4(+) T cells and Ig G/IgM(+) B cells. There were marked infiltrations of IgG(+) plasma cel ls around the lymphoid follicles. In contrast, the production of TNF-a lpha in the synovial fluid and the erythrocyte sedimentation rate (ESR ), which is a marker of systemic inflammatory activity in rheumatoid a rthritis, peaked at 6 h and 24 h, respectively, following the last inj ection of antigen. These values were also greater following the repeat ed injections of antigen compared with the single injection. The TNF-a lpha was produced markedly in the joints at the onset of the flare-ups of arthritis following the repeated injections of antigen, and the el evation of the ESR and an acceleration of the inflammatory response in the synovium were observed with a concomitant progression of severe a rticular destruction, suggesting that the marked production of TNF-alp ha at the time of flare-ups may be involved in the exacerbation of AIA in rabbits.