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INFLAMMATION AND IMMUNOPHARMACOLOGY

Ethanol Causes Inflammation in the Airways by a Neurogenic and TRPV1-Dependent Mechanism

Center of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, Italy (M.T., D.G., F.B., B.C., M.R., S.H.); Clinical Research Unit of Allergy, Charité School of Medicine, Berlin, Germany (Q.T.D., D.A.G., A.F.); Sanofi Recherche, Montpellier, France (X.E.-A.); CEA, Service de Pharmacologie et d'Immunologie, CEA-Saclay, Gif sur Yvette, France (C.C.); and Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy (P.G.)

Ethanol (EtOH) stimulates peptidergic primary sensory neurons via the activation of the transient receptor potential vanilloid-1 (TRPV1). EtOH is also known to trigger attacks of asthma in susceptible individuals. Our aim was to investigate whether EtOH produces airway inflammation via a TRPV1-dependent mechanism and to verify whether this effect is produced via a mechanism distinct from that of acetaldehyde (AcH). EtOH caused a Ca²⁺-dependent release of neuropeptides from guinea pigs airways, an effect that was inhibited by both capsaicin pretreatment and the TRPV1 antagonist capsazepine (CPZ). Furthermore, EtOH contracted isolated guinea pig bronchi, showing efficacy similar to that of carbachol: this effect of EtOH was sensitive to capsaicin pretreatment, tachykinin receptor blockade, and TRPV1 antagonism. The EtOH metabolite AcH also contracted isolated guinea pig bronchi, but this action was not affected by capsaicin pretreatment, tachykinin receptor, or TRPV1 antagonism. EtOH by intravenous or intragastric route of administration caused bronchoconstriction and increased plasma extravasation in the guinea pig airways, effects that were abolished selectively by CPZ. In conclusion, we have demonstrated that EtOH stimulates peptidergic primary sensory neurons in the guinea pig airways by TRPV1 activation. This excitatory effect of EtOH, distinct from that of AcH, results in neurogenic inflammatory responses that may contribute to the mechanism of EtOH-induced asthma.

Address correspondence to: Dr. Selena Harrison, Center of Excellence for the Study of Inflammation, University of Ferrara, 44100 Ferrara, Italy. E-mail: selena.harrison{at}unife.it

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