EFFECTS OF CAMP-PHOSPHODIESTERASE ISOZYME INHIBITOR ON CYTOKINE PRODUCTION BY LIPOPOLYSACCHARIDE-STIMULATED HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

1. The effects of cAMP-phosphodiesterase (PDE) isozyme inhibitors on t he production of tumor necrosis factor alpha (TNF-alpha), and interleu kins 1 beta and 8 (IL-1 beta and IL-8) by lipopolysaccharide (LPS)-sti mulated human peripheral blood mononuclear cells (PBMC) were evaluated . In addition, we investigated the effects of dibutyryl cAMP (dbcAMP) and beta-adrenergic receptor agonist on the production of these cytoki nes. 2. Type IV PDE inhibitors were more effective at inhibiting the p roduction of TNF-alpha and IL-1 beta by LPS-stimulated PBMC than a non selective, type III or type III/IV inhibitor. In contrast, these agent s had no effect on IL-8 production. 3. Increasing concentrations of db cAMP progressively reduced the production of TNF-alpha and IL-1 beta b ut not IL-8. 4. The addition of beta-agonist increased the inhibitory effect of PDE inhibitors tested on the production of TNF-alpha and IL- 1 beta. 5. Type IV PDE inhibitors could be potent pharmacological agen ts for the treatment of diseases in which TNF-alpha and IL-1 beta are important etiological factors. (C) 1997 Elsevier Science Inc.