SUPPRESSION OF IL-6 BIOLOGICAL-ACTIVITIES BY ACTIVIN-A AND IMPLICATIONS FOR INFLAMMATORY ARTHROPATHIES

Activin A is a cytokine whose multiple functions have yet to be fully determined. In this study, the role of proinflammatory cytokines in re gulatory control of activin A production was shown in synoviocytes and chondrocytes. Additional facets of functional inflammation-related ac tivities of activin A were also determined. Results showed that activi n A concentrations in the synovial fluid of patients with rheumatoid a rthritis and gout were elevated relative to those in patients with ost eoarthritis. Further studies showed that production of activin A by sy noviocytes and chondrocytes in culture was stimulated by cytokines suc h as IL-1, transforming growth factor-beta (TGF-beta), interferon-gamm a (IFN-gamma), and IL-8, consistent with previous studies in regard to the control of activin A production in marrow stromal cells and monoc ytes by cytokines, glucocorticoids and retinoic acid. In addition, the relationship of activin A to IL-6-induced biological activities was i nvestigated. Three major IL-6 activities involved in inflammatory resp onses were found to be suppressed by activin A. In a dose-dependent ma nner, activin A efficiently suppressed IL-6-induced proliferation of 7 TD1 B lymphoid cells, phagocytic activity of monocytic M1 cells, and f ibrinogen production in HepG2. Therefore, it is likely that activin A serves as a suppressor for IL-6, dampening inflammatory responses, and has the potential to perform some previously unrecognized roles in in flammation.