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Keywords:

  • antigen challenge;
  • bronchial hyperresponsiveness;
  • airway inflammation;
  • eosinophils;
  • neutrophils;
  • phosphodiesterase inhibitor;
  • KF19514;
  • olprinone;
  • methacholine;
  • 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.

Conclusion

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