Effect of aerosolized administration of KF19514, a phosphodiesterase 4 inhibitor, on bronchial hyperresponsiveness and airway inflammation induced byantigen inhalation in guinea-pigs

Background Although phosphodiesterase (PDE) 3 and 4 inhibitors have receive d much attention for the treatment of bronchial asthma, systemic adverse ef fects have also been reported. Objective The purpose of this study was to investigate the effect of inhale d olprinone, a newly developed PDE3 inhibitor, and KF19514, a PDE1 and 4 in hibitor, on antigen-induced airway reactions in guinea-pigs. Methods Fifteen minutes after inhalation of olprinone (0.1 or 1.0 mg/mL) an d KF19514 (0.1 or 0.01 mg/mL), animals were given an antigen challenge. Bro nchial hyper-responsiveness and bronchoalveolar lavage fluid cell analysis were performed 24 h after the antigen challenge. Results Inhalation of olprinone and KF19514 caused a dose-related inhibitio n of antigen-induced bronchoconstriction. Antigen inhalation significantly increased bronchoconstrictor responses to methacholine, and airway accumula tion of neutrophils and eosinophils, 24 h after the antigen challenge. Thes e responses were dose-dependently prevented by KF19514, but not by olprinon e. Conclusion The results indicate that inhaled PDE inhibitors might be useful for treatment of bronchial asthma.