title: Bronchodilator and Anti-Inflammatory Action of Theophylline in a Model of Ovalbumin-Induced Allergic Inflammation.
abstract: Phosphodiesterases (PDEs) represent a super-family of 11 enzymes hydrolyzing cyclic nucleotides into inactive 5' monophosphates. Inhibition of PDEs leads to a variety of cellular effects, including airway smooth muscle relaxation, inhibition of cellular inflammation, and immune responses. In this study we focused on theophylline, a known non-selective inhibitor of PDEs. Theophylline has been used for decades in the treatment of chronic inflammatory airway diseases. It has a narrow therapeutic window and belongs to the drugs whose plasma concentration should be monitored. Therefore, the main goal of this study was to evaluate the plasma theophylline concentration and to determine its relevance to pharmacological effects after single and longer term (7 days) administration of theophylline at different doses (5, 10, 20, and 50 mg/kg) in guinea pigs. Airway hyperresponsiveness was assessed by repeated exposure to ovalbumin. Theophylline reduced specific airway resistance in response to histamine nebulization, measured in a double chamber body plethysmograph. A decrease in tracheal smooth muscle contractility after cumulative doses of histamine and acetylcholine was confirmed in vitro. A greater efficacy of theophylline after seven days long treatment indicates the predominance of its anti-inflammatory activity, which may be involved in the bronchodilating action.
authors.affiliation: Department of Pharmacology and Biomed, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora, 03601, Martin, Slovakia. anna.urbanova@jfmed.uniba.sk.
authors.forename: A
authors.initials: A
authors.lastname: Urbanova
authors.affiliation: Department of Pharmacology and Biomed, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora, 03601, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Kertys
authors.affiliation: Institute of Clinical Biochemistry, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.|University Hospital Martin, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Simekova
authors.affiliation: Department of Physiology and BioMed, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Mikolka
authors.affiliation: Department of Physiology and BioMed, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Kosutova
authors.affiliation: Department of Physiology and BioMed, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Mokra
authors.affiliation: Department of Pharmacology and Biomed, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora, 03601, Martin, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Mokry
mesh_terms: D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010047:Ovalbumin / Q000633:toxicity; D010993:Plethysmography, Whole Body; D013806:Theophylline / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D010047:Ovalbumin; D013806:Theophylline
keywords: Airway reactivity; Allergic inflammation; Bronchial responsiveness; Guinea pigs; Organ bath; Phosphodiesterase inhibitors; Smooth muscle; Theophylline; Xanthine derivatives