Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients.
Oxidative stress associated with increased presence of neutrophils is an important feature of inflammatory airways diseases like asthma or chronic obstructive pulmonary disease. We studied the in vitro effect of piclamilast (RP73401), a selective phosphodiesterase (PDE)-4 inhibitor, compared to theophylline and prednisolone, on respiratory burst of sputum cells from mild asthmatics and COPD patients. Sputum cells were harvested from mild asthmatics and stable COPD patients and treated with piclamilast, theophylline or prednisolone. Respiratory burst was assessed by luminol-dependent chemoluminescence after stimulation with 10 microM n-formyl-met-leu-phe (FMLP). Piclamilast inhibited FMLP-induced respiratory burst of sputum cells in a concentration-dependent manner (asthma: EC50 approximately 100 nM, max. inhibition: 97.5+/-5% at 100 microM; COPD: EC50 approximately 1 microM, max. inhibition: 70.6+/-4.5% at 100 microM), whereas maximal inhibition observed with theophylline (asthma: max. inhib. 27+/-15%; COPD: 6+/-2%, both p < 0.05 vs. piclamilast) and prednisolone (asthma: 16+/-6%; COPD: 7.8+/-6.2%, both p < 0.05 vs. piclamilast) was weaker. Inhibition by piclamilast was largely reversed through pretreatment of cells with the adenylcyclase inhibitor SQ22536. We concluded that piclamilast, a selective PDE-4 inhibitor, attenuates the respiratory burst of sputum cells from mild asthmatics and COPD patients in vitro. These data underline the potential of PDE-4 inhibition as a novel therapeutic approach to inflammatory airway diseases like asthma or COPD.
Beeh
Kai M
KM
INSAF Respiratory Research Institute, Biebricher Allee 34, 65187 Wiesbaden, Germany. k.beeh@insaf-wi.de
Beier
Jutta
J
Lerch
Claudia
C
Schulz
Ann K
AK
Buhl
Roland
R
D000328:Adult; D001249:Asthma / Q000473:pathology*; D001549:Benzamides / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011239:Prednisolone / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology*; D016897:Respiratory Burst / Q000187:drug effects*; D013183:Sputum / Q000166:cytology; D013806:Theophylline / Q000494:pharmacology
D001549:Benzamides; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D011239:Prednisolone; D013806:Theophylline; C087566:piclamilast