Stimulus-specific inhibition of IL-5 by cAMP-elevating agents and IL-10 reveals differential mechanisms of action.

Interleukin-5 (IL-5) is a Th2 cytokine, which is implicated in the pathogenesis of eosinophilic diseases such as asthma. Peripheral blood mononuclear cells (PBMC), costimulated with phorbol 12-myristate 13-acetate (PMA) plus phytohemagglutinin (PHA) or activating antibodies to the CD3 and CD28 T-lymphocyte surface markers, produced similar patterns of IL-5 expression. However, in PMA + PHA-treated cells, 8-bromo-cAMP and PGE(2) did not affect IL-5 expression, whereas in CD3 + CD28-stimulated cells, almost total repression was observed. IL-10 failed to inhibit IL-5 mRNA from PMA + PHA-treated cells, yet reduced release by 40%. By contrast, IL-10 totally inhibited CD3 + CD28-induced IL-5 release and inhibited mRNA by 50-60%. These results highlight important biological differences in the induction of IL-5 by the nonspecific stimulus PMA + PHA and the more physiological CD3 + CD28 costimulation. Finally, the potential for downregulating Th2 responses by cAMP-elevating agents or IL-10 is demonstrated and a significant role for posttranscriptional mechanisms in the inhibition by IL-10 is suggested. Copyright 2000 Academic Press.