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

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.

• Authors: Heinz-Gerd Hoymann, Lutz Wollin, Meike Muller, Regina Korolewitz, Norbert Krug, Armin Braun, Rolf Beume
• Journal: Pharmacology (Pharmacology) Vol. 83 Issue 3 Pg. 188-95 ( 2009) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 19176983 (Publication Type: Journal Article)
• Copyright: 2009 S. Karger AG, Basel.

Chemical References

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

Topics

• Aminopyridines (pharmacology)
• Animals
• Antigens, Fungal (immunology)
• Aspergillus fumigatus (immunology)
• Asthma (drug therapy, metabolism, 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)