Asthma imposes considerable patient and economic burdens, with the most severe cases causing the greatest affliction. Identifying stimuli that worsen
asthma severity is an essential step to controlling both disease morbidity and the lessening economic impact. This study provides the first mechanistic investigation into how acute
ethanol exposure will increase
asthma severity in a murine model of mild
cockroach allergen (CRA)-induced
asthma. Outbred mice were sensitized to induce mild allergic
asthma, with intratracheal CRA exposures on days 0 and 14. On day 21 mice were gavaged with water or 32%
ethanol, and the third
allergen exposure was given 30 min post-gavage. Asthmatic responses were measured at several time-points up to 42 h after the third
allergen challenge.
Ethanol-gavaged mice showed increased
asthma severity within 90 min post-
allergen challenge, with exacerbations lasting for 24 h.
Ethanol caused greater airways obstruction, including an eightfold increase in epithelial cell
mucin and increased mucus plugs, resulting in a 50% reduction in bronchiole patency.
Ethanol gavage also induced significant increases in airways hyperreactivity. While T helper type 1 (Th1) and Th2
cytokines were not altered by
ethanol gavage, pulmonary neutrophil and eosinophil recruitment were augmented. This increase was associated with increased
chemokine production. Administration 2 h prior to
ethanol gavage of a
neutralizing antibody cocktail to keratinocyte-derived
chemokine, macrophage inflammatory protein-2,
eotaxin-1 and
eotaxin-2 prevented
ethanol-induced eosinophil recruitment and airways hyperreactivity. These data provide evidence that acute alcohol exposure immediately prior to a mild
allergen-triggered asthmatic episode will exacerbate
asthma severity mediated by increased production of
chemokines.