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

Clin Exp Allergy. 2000 May;30(5):713-8. doi: 10.1046/j.1365-2222.2000.00782.x.

Abstract

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.

Conclusion: The results indicate that inhaled PDE inhibitors might be useful for treatment of bronchial asthma.

Publication types

  • Comparative Study

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Administration, Inhalation
  • Aerosols
  • Animals
  • Antigens / administration & dosage*
  • Asthma / enzymology
  • Asthma / immunology
  • Asthma / pathology
  • Bronchial Hyperreactivity / enzymology
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / pathology*
  • Bronchial Hyperreactivity / prevention & control
  • Bronchial Provocation Tests
  • Bronchodilator Agents / administration & dosage*
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Guinea Pigs
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Male
  • Methacholine Chloride / administration & dosage
  • Naphthyridines / administration & dosage*
  • Naphthyridines / adverse effects
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Pyridones / administration & dosage
  • Pyridones / adverse effects

Substances

  • Aerosols
  • Antigens
  • Bronchodilator Agents
  • Imidazoles
  • KF 19514
  • Naphthyridines
  • Phosphodiesterase Inhibitors
  • Pyridones
  • Methacholine Chloride
  • olprinone
  • Ovalbumin
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4