Effects of cAMP-Phosphodiesterase Isozyme Inhibitor on Cytokine Production by Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells

• Published in: General pharmacology 1997-10, Vol.29 (4), p.633-638
• Main Authors: Yoshimura, Tomoaki, Kurita, Chikako, Nagao, Tomomi, Usami, Eiseki, Nakao, Toshiya, Watanabe, Shino, Kobayashi, Joji, Yamazaki, Futoshi, Tanaka, Hiroyuki, Nagai, Hiroichi
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology; Aminophylline - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Bucladesine - pharmacology; cAMP; Cytokines - blood; Humans; In Vitro Techniques; Interleukin-1 - metabolism; interleukin-1β; interleukin-8; Interleukin-8 - metabolism; Isoenzymes - antagonists & inhibitors; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lipopolysaccharides - pharmacology; Medical sciences; Milrinone; mononuclear cells; Naphthyridines - pharmacology; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase isozyme inhibitor; Purinones - pharmacology; Pyridones - pharmacology; Pyrrolidinones - pharmacology; Rolipram; Terbutaline - pharmacology; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factor-α
• ISSN: 0306-3623; 1879-0011
• DOI: 10.1016/S0306-3623(96)00580-0

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.