Effects of the phosphodiesterase type 4 inhibitor roflumilast on early and late allergic response and airway hyperresponsiveness in Aspergillus-fumigatus-sensitized mice.
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.
Hoymann
Heinz-Gerd
HG
Fraunhofer Institute of Toxicology and Experimental Medicine (Fraunhofer ITEM), Hannover, Germany. heinz-gerd.hoymann@item.fraunhofer.de
Wollin
Lutz
L
Muller
Meike
M
Korolewitz
Regina
R
Krug
Norbert
N
Braun
Armin
A
Beume
Rolf
R
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001549:Benzamides / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003521:Cyclopropanes / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D005260:Female; D007958:Leukocyte Count; D008214:Lymphocytes / Q000166:cytology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology; D058988:Phosphodiesterase 4 Inhibitors; D011014:Pneumonia / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000188:drug therapy; D015656:Respiratory Mechanics / Q000187:drug effects*
D000631:Aminopyridines; D000946:Antigens, Fungal; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast; D016210:Methacholine Chloride