Abstract
Abstract Contributors to the development of atopic asthma can be multifactorial, with severe cases often requiring several stimuli, including allergen, LPS, and environmental factors. Here we show that alcohol intoxication concurrent with cockroach allergen (CRA) exposure will cause significant asthmatic exacerbations in mice pre-sensitized to CRA. CRA exposures were given on days 0 and 14, then outbred mice were gavaged with water or 32% ethanol on day 21 and challenged with CRA 30 minutes post-gavage. Kinetics of asthmatic inflammation were investigated. Ethanol intoxication significantly increased eotaxins and CXC chemokines in the bronchoalveolar lavage (BAL), peaking 90 minutes post-CRA challenge. Ethanol-gavaged mice displayed 2-fold increases in BAL eosinophils and 3-fold increases in BAL neutrophils over water-gavaged controls by 16 hours post-allergen challenge. Ethanol also resulted in significant respiratory impairment, including an acute 3-fold increase in airways mucin, increased mucus plug formation and bronchiole occlusion, and a 2-fold increase in airways hyperreactivity 14 hours post-CRA challenge. Pre-administration of a cocktail of neutralizing antibodies to eotaxins and CXC chemokines reduced BAL cellular infiltrate to baseline levels and decreased airways hyperreactivity by 50%. These data provide evidence that alcohol intoxication can exacerbate asthmatic inflammation and respiratory function, which may be mediated by ethanol-induced chemokine production.
Published Version
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