Effects of phosphodiesterase inhibitors on secretions of human monokines

Abstract

The purpose of this study was to evaluate the effect of newly developed selective phosphodiesterase (PDE) inhibitors, KF19514 (type l/IV) and cilostazol (type III), and theophylline on the secretions of tumor necrosis factor a (TNFα) and interleukin-1β (IL-1 β) from human peripheral monocytes stimulated by lipopolysaccha- ride (LPS). Human blood monocytes were incubated with LPS in the absence or presence of KF19514, cilostazol or theophylline. TNFα and IL-1in the cell- free supernatants were measured with enzyme-linked immunosorbent assay. KF19514 showed significant inhibition on the release of TNFα (% inhibition ± SEM was 82.8 ± 7.4% at 1 nmol/L) and IL-1 β (34.4 ± 7.5% at 10 (μmol/L). In addition, KF19514 inhibited the expression of TNFa mRNA. Cilostazol inhibited the release of TNFa significantly (60.2 ± 8.9% at 30 μmol/L) but not IL-1 β. Theophylline inhibited slightly but significantly the release of TNFa at a therapeutic concentration (1 7.4 ± 5.1% at 100 μmol/L). These results suggest that theophylline may not only have a bronchodilating action but also an anti-inflammatory property in the treatment of bronchial asthma, and that KF19514 may have an anti-inflammatory action on at least the transcriptional level.

Keywords

• cilostazol
• interleukin-JB
• KF19514
• monocytes
• phosphodiesterase inhibitor
• theophylline
• tumor necrosis factor α