Regulation of interleukin 6 production in T helper cells

The cytokine interleukin 6 (IL-6) is a cellular regulatory molecule that is produced by both lymphoid and non-lymphoid cells in response to several stimuli. In this report we present evidence that within the murine T cell compartment T helper type 2 cells (Th2) produce this lymphokine, whereas unprimed CD4+ T cells and a T helper type 1 clone (Th1) do not. Furthermore, IL-6 is not an autocrine growth factor for in vitro cultured Th cells, in contrast to what occurs in freshly isolated CD4+ and CD8+ T cells. We have examined the signal transduction pathways that lead to IL-6 production in activated Th2 cells. We have found that protein kinase C activators, such as PMA, Con A, or IL-1, increase the IL-6 expression in these cells. On the other hand, activation of the cAMP-dependent pathway does not seem to have an effect on the IL-6 production, since forskolin, 8BrcAMP, or TNF-alpha, which in these cells increases the level of intracellular cAMP, do not lead to an accumulation of IL-6 message. These results indicate that the IL-6 gene is more tightly regulated in T cells than in other systems described previously.