Effects of the phosphodiesterase type 4 inhibitor roflumilast on early and late allergic response and airway hyperresponsiveness in Aspergillus-fumigatus-sensitized mice

Pharmacology. 2009;83(3):188-95. doi: 10.1159/000196814. Epub 2009 Jan 29.

Abstract

Background: Inhibitory effects of roflumilast on responses characteristic of allergic asthma were investigated in a fungal asthma model in BALB/c mice.

Methods: Mice were sensitized with Aspergillus antigen (Afu) and exposed to Afu or vehicle, and given roflumilast 1 or 5 mg/kg. Early airway response (EAR) and late airway hyperresponsiveness (AHR) to methacholine were measured via plethysmography. Bronchoalveolar lavage (BAL) was used to assess inflammatory cell count.

Results: In Afu-exposed mice, roflumilast dose-dependently reduced the EAR [26% at 1 mg/kg (NS) and 94% at 5 mg/kg (p < 0.01)] and AHR [46% at 1 mg/kg (NS) and 128% at 5 mg/kg (p < 0.05)]. Roflumilast 5 mg/kg reduced neutrophil, eosinophil and lymphocyte counts [87% (p < 0.01), 40% (NS) and 67% (p < 0.01), respectively] in BAL fluid versus controls.

Conclusions: In this model, roflumilast inhibited the EAR, suppressed AHR and reduced inflammatory cell infiltration.

MeSH terms

  • Aminopyridines / pharmacology*
  • Animals
  • Antigens, Fungal / immunology*
  • Aspergillus fumigatus / immunology*
  • Asthma / drug therapy
  • Asthma / metabolism
  • Asthma / physiopathology
  • Benzamides / pharmacology*
  • Bronchial Hyperreactivity / drug therapy
  • Bronchoalveolar Lavage Fluid / cytology
  • Cyclopropanes / pharmacology
  • Disease Models, Animal
  • Eosinophils / cytology
  • Female
  • Leukocyte Count
  • Lymphocytes / cytology
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / cytology
  • Phosphodiesterase 4 Inhibitors*
  • Pneumonia / metabolism
  • Respiratory Hypersensitivity / drug therapy
  • Respiratory Mechanics / drug effects*

Substances

  • Aminopyridines
  • Antigens, Fungal
  • Benzamides
  • Cyclopropanes
  • Phosphodiesterase 4 Inhibitors
  • Roflumilast
  • Methacholine Chloride