Cytokine production by synovial T cells in rheumatoid arthritis

Objective. To investigate the production of cytokines by T cells in patient s with rheumatoid arthritis (RA), reactive arthritis (REA) and osteoarthrit is (OA). Methods. The lymphokines interleukin (IL)-2, IL-4, interferon gamma (IFN-ga mma) and tumour necrosis factor beta (TNF-beta), as well as the monokines I L-1, IL-6 and TNF-alpha, were measured by immunoassays in sera and synovial fluid (SF) from patients with RA, REA and OA. In addition, cytokine expres sion was studied by immunohistochemistry in synovial membrane tissue sectio ns from patients with RA and OA. Results. Almost 60% of RA sera contained at least one of the cytokines inve stigated, though in low concentrations, whereas cytokines were generally no t detectable in sera from REB and OA patients. In contrast, cytokines were found in virtually all SF; thus, the majority of SF from RA patients contai ned IFN-gamma (median level 17 pg/ml) in addition to the monokines IL-6 (47 00 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not TNF-alpha) were also frequently measured in SF from REA patients, whereas OA samples typically contained only IL-6. Immunohistochemical analysis of tissue secti ons from RA patients revealed lymphokine expression in 0.1-0.3% of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also IL-4. Interes tingly, the expression of TNF-alpha and IL-6 by synovial T cells was also o bserved. The majority of cytokine-expressing T cells were CD4-positive T-he lper cells typically found in perivascular areas, whereas cytokine-producin g CD8-positive T cells were found distributed throughout the synovium. As e xpected, in specimens from OA patients, T cells were much less abundant and expression of cytokines could not be detected. Conclusion. These data clearly demonstrate production of cytokines by T cel ls in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.