Ew. Yu et al., SUPPRESSION OF IL-6 BIOLOGICAL-ACTIVITIES BY ACTIVIN-A AND IMPLICATIONS FOR INFLAMMATORY ARTHROPATHIES, Clinical and experimental immunology, 112(1), 1998, pp. 126-132
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.