Effect of aerosolized administration of KF19514, a phosphodiesterase 4 inhibitor, on bronchial hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea-pigs.
BACKGROUND
Although phosphodiesterase (PDE) 3 and 4 inhibitors have received much attention for the treatment of bronchial asthma, systemic adverse effects have also been reported.


OBJECTIVE
The purpose of this study was to investigate the effect of inhaled olprinone, a newly developed PDE3 inhibitor, and KF19514, a PDE1 and 4 inhibitor, on antigen-induced airway reactions in guinea-pigs.


METHODS
Fifteen minutes after inhalation of olprinone (0.1 or 1.0 mg/mL) and KF19514 (0.1 or 0.01 mg/mL), animals were given an antigen challenge. Bronchial 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 inhibition of antigen-induced bronchoconstriction. Antigen inhalation significantly increased bronchoconstrictor responses to methacholine, and airway accumulation of neutrophils and eosinophils, 24 h after the antigen challenge. These responses were dose-dependently prevented by KF19514, but not by olprinone.


CONCLUSIONS
The results indicate that inhaled PDE inhibitors might be useful for treatment of bronchial asthma.
Myou
S
S
The Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Ishikawa, Japan.
Fujimura
M
M
Kurashima
K
K
Tachibana
H
H
Hirose
T
T
Nakao
S
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006168:Guinea Pigs; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D009287:Naphthyridines / Q000008:administration & dosage* / Q000009:adverse effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects
D000336:Aerosols; D000941:Antigens; D001993:Bronchodilator Agents; D007093:Imidazoles; C106878:KF 19514; D009287:Naphthyridines; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D016210:Methacholine Chloride; C059498:olprinone; D010047:Ovalbumin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4