Divergent cell-specific effects of activin-A on thymocyte proliferation stimulated by phytohemagglutinin, and interleukin 1beta or interleukin 6 in vitro

Activin-A is a member of the transforming growth factor-beta (TGF-beta) cytokine family. Based on studies in several cell systems, activin-A has been postulated to be a specific inhibitor of the actions of the inflammatory cytokine, interleukin 6. In cultures of adult rat thymocytes, activin-A inhibited sub-optimal phytohemagglutinin-induced and interleukin 1beta-stimulated proliferation, as measured by [(3)H]-thymidine incorporation in vitro. In contrast with TGF-beta1, which exerted similar inhibitory effects on thymocyte proliferation, activin-A activity was reduced by increasing the concentration of phytohemagglutinin or addition of the reducing agent, beta-mercaptoethanol. Both activin-A and TGF-beta1 inhibited the in vitro production of interleukin 6 by thymocytes in the presence of phytohemagglutinin and interleukin 1beta. In the presence of exogenous interleukin 6, however, both activin-A and TGF-beta1 stimulated thymocyte proliferation. These data suggest that activin-A inhibits thymocyte growth and differentiation, at least in part, by inhibiting endogenous production of interleukin 6, but stimulates thymocyte growth when exogenous interleukin 6 is present in vitro. These data indicate that activin interacts with other cytokines to exert complex regulation of T cell development, and is not an inhibitor of interleukin 6 action in all cell systems.