Inhibitor of interleukin-2 in rheumatoid synovial fluid

Although large numbers of T cells infiltrate the synovium of patients with rheumatoid arthritis (RA), the responses of these cells, as present in the blood and synovial fluid (SF), to exogenous interleukin-2 (IL-2) and their production of IL-2 are diminished. To investigate this functional defect, RA SF were examined for the presence of inhibitors of IL-1 and IL-2. A factor was found which inhibited the IL-2-induced proliferation of mitogen-stimulated human T cells and the IL-1-induced proliferation of C3H/Hej mouse thymocytes, but not IL-1-induced fibroblast proliferation. On AcA 54 Ultrogel filtration, the inhibitory activity resided in a fraction with an apparent molecular weight of greater than 70 kd and a major pI of 6.8. The inhibitory effect of RA SF on lymphocyte proliferation was partially corrected with IL-2, but not with IL-1. In the presence of RA SF, normal lymphocytes showed not only a decreased response to exogenous IL-2, but also a decreased production of IL-2. The presence of an inhibitor of IL-2 in RA SF could contribute to the IL-2-related T cell defects observed in RA.