Effects of roflumilast on early and late allergic response and airway hyperresponsiveness in Aspergillus fumigatus-sensitized mice

H. G. Hoymann,1 R. Korolewitz,1 A. Braun,1 N. Krug,1 L. Wollin,2 R. Beume.2

Author address: 

1Exp. Airway Pharmacol., Fraunhofer Inst. of Toxicology and Experimental Medicine, Hannover, Germany; 2ALTANA Pharma AG, Konstanz, Germany

Abstract: 

Rationale Roflumilast is an investigational PDE4 inhibitor for potential asthma therapy. Inhibitory effects of roflumilast on allergen-induced early airway response (EAR), late airway hyperresponsiveness (AHR), and inflammatory cells were investigated in a fungal allergen model of asthma in BALB/c mice. Methods Mice were sensitized with Aspergillus fumigatus extract (Afu) and adjuvant (i.p. and s.c. both on Day 0). After 2 inhalation boosts with Afu aerosol on Days 14 and 21, animals were Afu aerosol challenged on Day 23. Before each Afu aerosol exposure, animals received i.g. 1mg/kg or 5mg/kg roflumilast. For EAR, lung resistance was measured by body plethysmography in orotracheally intubated mice. AHR against aerosolized methacholine was determined 24 h after challenge by head-out plethysmography. Bronchoalveolar lavage (BAL) was done 25 h after challenge and differential cell count was determined. Results Afu-sensitized and -challenged mice showed pronounced EAR, AHR, and pulmonary infiltration of inflammatory cells compared with vehicle-challenged animals. Roflumilast 1mg/kg and 5mg/kg dose-dependently inhibited EAR (26%, n.s. and 94%, p
2005

abstract No: 

1391

Full conference title: 

15th European Respiratory Society annual conference
    • ERS 15th (2005)