title: Influence of roflumilast on airway reactivity and apoptosis in ovalbumin-sensitized Guinea pigs.
abstract: Chronic inflammatory diseases, associated with airway obstruction and cough, are usually treated with bronchodilating and anti-inflammatory drugs. Inhibition of phosphodiesterases (PDE) leads to both of these effects and influences apoptosis of immune cells. In chronic obstructive pulmonary disease, roflumilast, a selective PDE4 inhibitor, has been recently approved for pharmacotherapy. The aim of this study was to evaluate the effect of long-term administration of roflumilast in experimental allergic inflammation in guinea pigs. Male adult guinea pigs were used in the study. There were four experimental groups sensitized with ovalbumin for 14 days and thereafter treated per os, by inhalation, and intraperitoneally for 7 days with roflumilast or vehicle. A control group was left without sensitization. Roflumilast reduced specific airway resistance after nebulization of histamine, as measured in a double-chamber whole-body plethysmograph. This effect was confirmed in in vitro organ bath, with significant decreases in tracheal and lung smooth muscle contractility after cumulative doses of histamine. Suppression of hematological and immunological markers of inflammation and enhanced apoptosis in animals treated with roflumilast points to the possibility of a beneficial effect of roflumilast in allergic inflammation.
authors.affiliation: Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, 26 Sklabinska, 03601, Martin, Slovakia, medvedova@jfmed.uniba.sk.
authors.forename: I
authors.initials: I
authors.lastname: Medvedova
authors.forename: M
authors.initials: M
authors.lastname: Prso
authors.forename: A
authors.initials: A
authors.lastname: Eichlerova
authors.forename: D
authors.initials: D
authors.lastname: Mokra
authors.forename: P
authors.initials: P
authors.lastname: Mikolka
authors.forename: J
authors.initials: J
authors.lastname: Mokry
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000403:Airway Resistance / Q000187:drug effects*; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003521:Cyclopropanes / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010047:Ovalbumin; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D010993:Plethysmography, Whole Body; D061251:Primary Cell Culture; D046509:Tissue Culture Techniques
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast; D006632:Histamine; D010047:Ovalbumin