Transforming growth factor-beta 1 (TGF-beta 1) inhibits DNA synthesis of PWM-stimulated PBMC via suppression of IL-2 and IL-6 production.

The multifunctional cytokine transforming growth factor-beta 1 (TGF-beta 1) is known to inhibit the proliferation of lymphocytes. However, the role of TGF-beta 1 in the production and secretion of various interleukins is not yet clear. In this study we have analysed in parallel the effects of TGF-beta 1 on both DNA synthesis and production of the cytokines IL-1, IL-2, IL-6, and TNF-alpha by pokeweed mitogen-stimulated peripheral blood mononuclear cells. With this stimulation system we show that TGF-beta 1 at a concentration of 15 ng/ml significantly suppresses IL-2 and IL-6 production. The release of IL-1 and TNF-alpha, however, was not influenced under these conditions. Under similar conditions DNA synthesis of PWM-stimulated PBMC was found to be inhibited by 50 +/- 10%. Using flow cytometric methods we could demonstrate that TGF-beta 1 arrested the cells in the G0/G1 phase of the cell cycle. Taken together, these results suggest that TGF-beta 1 may suppress immune responses by inhibiting the endogenous production of IL-2 and IL-6.