IL-2 induces IL-6 production in human monocytes

IL-2 is a potent activator of effector and secretory activities of human monocytes. Since monocytes are an important source of IL-6, we investigated whether IL-2 can induce IL-6 production and whether regulatory circuits can modulate this process. We found that stimulation of monocytes with IL-2 induced expression of IL-6 mRNA and bioactivity in a dose-dependent manner. Production of IL-6 in monocytes can be induced by other cytokines such as IL-1β. By using mAb α-IL-1β we showed that IL-2-induced IL-6 production is not mediated by the autocrine stimulation of IL-1β elicited by IL-2. IL-6 induction by monocytes is not a common response to activating signals because IFN-γ did not induce IL-6 expression under conditions in which it elicits tumoricidal activity. In contrast, IFN-γ could completely abrogate the induction of IL-6 expression by IL-1β but did not affect the levels of mRNA and the secretion of IL-2-elicited IL-6. We have previously reported that transforming growth factor-β inhibits IL-6 production in response to IL-1β. Studies on the inhibitory activity of transforming growth factor-β demonstrated that this cytokine differs from IFN-γ because it inhibited both IL-1- and IL-2-induced IL-6 expression. These data demonstrate that, in human monocytes, both IL-1 and IL-2 stimulate IL-6 expression by independent mechanisms that can be dissociated by the susceptibility to the inhibitory effect of IFN-γ. IL-6 production is also down-regulated by TGF-β, whose inhibitory activity is stimulus-unrelated.