Effects of cAMP-phosphodiesterase isozyme inhibitor on cytokine production by lipopolysaccharide-stimulated human peripheral blood mononuclear cells.

Abstract 1. The effects of cAMP-phosphodiesterase (PDE) isozyme inhibitors on the production of tumor necrosis factor α (TNF-α), and interleukins 1β and 8 (IL-1β and IL-8) by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC) were evaluated. In addition, we investigated the effects of dibutyryl cAMP (dbcAMP) and β-adrenergic receptor agonist on the production of these cytokines. 2. Type IV PDE inhibitors were more effective at inhibiting the production of TNF-α and IL-1β by LPS-stimulated PBMC than a nonselective, type III or type III/IV inhibitor. In contrast, these agents had no effect on IL-8 production. 3. Increasing concentrations of dbcAMP progressively reduced the production of TNF-α and IL-1β but not IL-8. 4. The addition of β-agonist increased the inhibitory effect of PDE inhibitors tested on the production of TNF-α and IL-1β. 5. Type IV PDE inhibitors could be potent pharmacological agents for the treatment of diseases in which TNF-α and IL-1β are important etiological factors.