Acute oral ethanol exposure triggers asthma in cockroach allergen-sensitized mice.
Asthma may be triggered by multiple mediators, including allergen-IgE cross-linking and non-IgE mechanisms. Several clinical studies have shown acute ethanol consumption exacerbates asthma, yet no animal model exists to study this process. We developed a model of ethanol-triggered asthma in allergen-sensitized mice to evaluate the mechanisms of ethanol inducing asthma-like responses. Outbred mice were exposed to cockroach allergens on Days 0 and 14; and on Day 21, mice received ethanol by oral gavage. Tracer studies confirmed alcohol aspiration did not occur. Within 30 minutes, alcohol induced degranulation of over 74% of mast cells, and multiple parameters of asthma-like pulmonary inflammation were triggered. Ethanol-gavaged mice had a fivefold increased production of eotaxin-2 (534 pg/mL) and a sevenfold increase in bronchoalveolar eosinophils (70,080 cells). Ethanol induced a 10-fold increase in IL-13, from 84 pg/mL in sensitized mice to 845 pg/mL in ethanol-gavaged sensitized mice. In cockroach allergen-sensitized mice, ethanol triggered asthma-like changes in respiratory physiology and a significant fivefold increase in airway mucin production. Importantly, none of these asthmatic exacerbations were observed in normal mice gavaged with ethanol. Cromolyn sodium effectively stabilized mast cells, yet increased mucin production and bronchoalveolar eosinophil recruitment. Together, these data show a single oral alcohol exposure will trigger asthma-like pulmonary inflammation in allergen-sensitized mice, providing a novel asthma model.
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Massachusetts, USA.
Jacqueline C
JC
Bouchard
Jiyoun
J
Kim
Dominic R
DR
Beal
Louis J
LJ
Vaickus
Florin L
FL
Craciun
Daniel G
DG
Remick
D000284:Administration, Oral; D000428:Alcohol Drinking / Q000473:pathology; D000435:Alcoholic Intoxication / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015550:Cell Degranulation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004804:Eosinophils / Q000473:pathology; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008407:Mast Cells / Q000473:pathology / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009077:Mucins / Q000096:biosynthesis; D011014:Pneumonia / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012129:Respiratory Function Tests; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D009077:Mucins; C060835:allergen CRa, cockroach; D000431:Ethanol