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-be ta 1) is known to inhibit the proliferation of lymphocytes, Whether th is effect is a result of a direct action of TGF-beta(1) or an involvem ent of other ''immunoinhibitory'' cytokines is not yet clear. Here we have analyzed the effects of TGF-beta(1) on IL-10 and IL-1RA productio n in pokeweed mitogen-stimulated peripheral blood mononuclear cells (P BMC) and purified T lymphocytes. We show in these systems that TGF-bet a(1) at a concentration of 10 ng/ml significantly suppresses both IL-1 0 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 o f IL-10 by T lymphocytes in an additive manner. However, TGF-beta(1) d id not influence IL-1RA production in PWM-stimulated PBMC. The present data show that the inhibitory effect of TGF-beta(1) on mitogen-activa ted immune cells is not the consequence of induction of the inhibitory cytokines IL-10 or IL-PRA but rather an inhibitory action on the prod uction of IL-2 and/or IL-6.