REGULATION OF INTERLEUKIN-6 PRODUCTION IN T-HELPER CELLS

The cytoklne Interieukin 6 (IL-6) is a cellular regulatory molecule that Is produced by both lymphold and non-lymphold cells In response to several stimuli. In this report we present evidence that within the murlne 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 transductlon pathways that lead to IL-6 production In activated Th2 cells. We have found that protein klnase 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 forskolln, SBrcAMP, or TNF-α, 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. © 1990 Oxford University Press.