TRANSFORMING GROWTH-FACTOR BETA(1) INHIBITS INTERLEUKIN-1O MESSENGER-RNA EXPRESSION AND PRODUCTION IN POKEWEED MITOGEN-STIMULATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND T-CELLS

The multifunctional cytokine transforming growth factor-beta(1)(TGF-beta 1) is known to inhibit the proliferation of lymphocytes, Whether this effect is a result of a direct action of TGF-beta(1) or an involvement of other ''immunoinhibitory'' cytokines is not yet clear. Here we have analyzed the effects of TGF-beta(1) on IL-10 and IL-1RA production in pokeweed mitogen-stimulated peripheral blood mononuclear cells (PBMC) and purified T lymphocytes. We show in these systems that TGF-beta(1) at a concentration of 10 ng/ml significantly suppresses both IL-10 mRNA expression and IL-10 production. IL-2 and IL-6 were capable of abolishing the effect of TGF-beta(1) on DNA synthesis and production of IL-10 by T lymphocytes in an additive manner. However, TGF-beta(1) did not influence IL-1RA production in PWM-stimulated PBMC. The present data show that the inhibitory effect of TGF-beta(1) on mitogen-activated immune cells is not the consequence of induction of the inhibitory cytokines IL-10 or IL-PRA but rather an inhibitory action on the production of IL-2 and/or IL-6.