MODULATION OF TH1-LIKE AND TH2-LIKE CYTOKINE PRODUCTION FROM MITOGEN-STIMULATED HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS BY PHOSPHODIESTERASE INHIBITORS

1. Effects of phosphodiesterase (PDE) inhibitors on the production of IFN-gamma, IL-2, IL-4 and IL-5 by phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) were investigated. In addition, we investigated the effects of dibutyrylcyclic AMP (dbcAMP) and a beta-adrenoceptor agonist on production of these cytokines. 2. T ype IV, type III and nonselective PDE inhibitors were effective at inh ibiting the production of IFN-gamma and IL-2 production in a dose depe ndent manner. In contrast, IL-4 and IL-5 production was inhibited by o nly the highest concentration of type IV inhibitor, and other agents h ad no effect on the production. 3. Similarly, dbcAMP inhibited the pro duction of IFN-gamma and IL-2 more potently than IL-4 and IL-5. 4. The addition of a beta-adrenoceptor agonist increased the inhibitory effe ct of PDE inhibitors tested on the production of IFN-gamma and IL-2. 5 . These results indicate that PDE inhibitors or cAMP elevating agents modulate Th1 cytokine more effectively than Th2 cytokine production. ( C) 1998 Elsevier Science Inc.