title: Isbufylline, a new xanthine derivative, inhibits airway hyperresponsiveness and airway inflammation in guinea pigs.
abstract: The pharmacological actions of the new xanthine, isbufylline, were evaluated in several models of airway hyperresponsiveness and airway inflammation in guinea pigs. At a dose (106 mumol kg-1 i.p.) providing complete protection against acetylcholine aerosol-induced dyspnea in the guinea pig, isbufylline inhibited platelet activating factor (PAF)- and antigen-induced eosinophil infiltration into bronchoalveolar lavage fluid 24 h after challenge of normal and actively immunized guinea pigs, respectively. In addition, this dose of isbufylline also inhibited capsaicin-induced extravasation of protein into bronchoalveolar lavage fluid. Isbufylline, 4.2 mumol kg-1 i.v., significantly inhibited PAF-induced bronchial hyper-responsiveness to i.v. histamine, without exerting evident bronchodilator activity. On the other hand the bronchodilator, salbutamol, at a dose (10.4 mumol kg-1 i.p.) shown to be equieffective to isbufylline (106 mumol kg-1 i.p.) for blocking acetylcholine aerosol-induced dyspnea, had no protective action against PAF- or antigen-induced eosinophil recruitment in bronchoalveolar lavage fluid, or against capsaicin-induced plasma protein extravasation. Furthermore, salbutamol (3.5 mumol kg-1) significantly potentiated allergen-induced cell infiltration and PAF-induced bronchial hyperresponsiveness. The results suggest that isbufylline can exert significant anti-inflammatory actions in guinea pig airways, in addition to its bronchodilator activity. These pharmacological activities are not shared by the beta 2-adrenoceptor agonist, salbutamol.
authors.affiliation: Instituto Farmacobiologico Malesci, Pharmacology Department, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Manzini
authors.forename: F
authors.initials: F
authors.lastname: Perretti
authors.forename: L
authors.initials: L
authors.lastname: Abelli
authors.forename: S
authors.initials: S
authors.lastname: Evangelista
authors.forename: E A
authors.initials: EA
authors.lastname: Seeds
authors.forename: C P
authors.initials: CP
authors.lastname: Page
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000109:Acetylcholine / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002211:Capsaicin / Q000494:pharmacology; D003911:Dextrans; D004417:Dyspnea / Q000139:chemically induced / Q000517:prevention & control*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D010047:Ovalbumin / Q000633:toxicity; D010972:Platelet Activating Factor / Q000494:pharmacology
chemical_list: D001993:Bronchodilator Agents; D003911:Dextrans; D010972:Platelet Activating Factor; C015219:fluorescein isothiocyanate dextran; D006632:Histamine; D010047:Ovalbumin; C058878:isbufylline; D016650:Fluorescein-5-isothiocyanate; D000109:Acetylcholine; D000420:Albuterol; D002211:Capsaicin; D015056:1-Methyl-3-isobutylxanthine