Transforming Growth Factor β 1 Inhibits Interleukin-10 mRNA Expression and Production in Pokeweed Mitogen-Stimulated Peripheral Blood Mononuclear Cells and T Cells

The multifunctional cytokine transforming growth factor-β₁ (TGF-β₁) is known to inhibit the proliferation of lymphocytes. Whether this effect is a result of a direct action of TGF-β₁ or an involvement of other "immunoinhibitory" cytokines is not yet clear. Here we have analyzed the effects of TGF-β₁ 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-β₁ 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-β₁ on DNA synthesis and production of IL-10 by T lymphocytes in an additive manner. However, TGF-β₁ did not influence IL-1RA production in PWM-stimulated PBMC. The present data show that the inhibitory effect of TGF-β₁ on mitogen-activated immune cells is not the consequence of induction of the inhibitory cytokines IL-10 or IL-1RA but rather an inhibitory action on the production of IL-2 and/or IL-6.