Theophylline inhibits free oxygen radicals production by human monocytes via phosphodiesterase inhibition.
Recent evidence suggests that theophylline, apart from bronchodilatation, derives its therapeutic activity in asthma from anti-inflammatory effects. Free oxygen radicals play important role in the perpetuation of inflammatory processes underlying bronchoconstriction and airway hyperresponsiveness in asthmatics. In our previous studies, we have analyzed the immunomodulatory effects of theophylline on human monocyte metabolic activity and showed that theophylline in doses of 5-20 microg/ml inhibited the process of zymosan-induced activation, decreasing total and maximum O2- production. The aim of present study was to analyze the mechanism of theophylline action on human monocytes. Therefore, the effects of papaverine--a phosphodiesterase inhibitor, LAS 31025--selective phosphodiesterase IV inhibitor, 8-phenyltheophylline--A1 and A2 adenosine receptors antagonist, and 8-cyclopenthyl-1, 3 dipropylxanthine--selective A1 receptor antagonist on O2- release were assessed. Adenosine receptor antagonist exerted no influence, while papaverine and LAS 31025 suppressed spontaneous, zymosan-induced total and maximum O2- production. The suppressant effect was concentration-dependent. We conclude that theophylline in therapeutic and subtherapeutic concentrations suppresses human monocyte metabolic activity via phosphodiesterase inhibition.
Chorostowska-Wynimko
J
J
Laboratory of Molecular Diagnostics, Department of Lung Diseases, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. j.chorostowska@igichp.edu.pl
Kus
J
J
Skopińska-Rózewska
E
E
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D010726:Phosphodiesterase Inhibitors; D017382:Reactive Oxygen Species; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D010208:Papaverine; C028322:8-phenyltheophylline; D010727:Phosphoric Diester Hydrolases