late airway obstruction and neutrophil infiltration in sensitized mice after antigen provocation were suppressed by selective and non-selective phosphodiesterase inhibitors

Suppression of antigen-induced late airway obstruction associated with neutrophilic inflammation by selective and non-selective phosphodiesterase (PDE) inhibitors was investigated in mice. Respiratory resistance (Rrs) increased in sensitized BDF1 mice 4-6 h after antigen provocation, whereas no obvious immediate reaction was observed. This reaction was associated with marked airway neutrophilia without significant infiltration of eosinophils. A selective PDE IV inhibitor, T-440 (10-30 mg/kg), and a non-selective PDE inhibitor, theophylline (10 mg/kg), significantly inhibited airway obstruction and neutrophilia when administered orally. An anti-allergic drug, ketotifen (1 mg/kg), caused slight inhibition of airway obstruction, whereas it did not affect airway neutrophilia. These results suggest that neutrophilic inflammation plays a role in the airway obstructive reaction and that PDE has a regulatory role in obstructive airway disease associated with airway inflammation.