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

: Hoymann, H.-G.; Wollin, L.; Müller, M.; Korolewitz, R.; Krug, N.; Braun, A.; Beume, R.


Pharmacology 83 (2009), No.3, pp.188-195
ISSN: 0031-7012
ISSN: 1423-0313
Journal Article
Fraunhofer ITEM ()
airway hyperresponsiveness; allergic response; asthma - mouse; chronic obstructive pulmonary disease; Phosphodiesterase type 4 inhibitor; pulmonary function; roflumilast - anti-inflammatory effect

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