Gastroesophageal reflux-associated aspiration alters the immune response in asthma
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A large number of studies point toward chronic aspiration associated with gastroesophageal reflux disease (GERD) as an important factor involved in the development of asthma, the incidence of which has increased dramatically in industrially developed countries. Recent work suggests that medical intervention aimed at acid blockade is not sufficient to relieve the effects of chronic aspiration on asthma pathology, leaving surgical treatment of the disease as one of the few remaining options. This study examined the effect of chronic aspiration on the airway-associated immune response to allergens using a model of experimentally induced airway hypersensitivity in Balb/c mice.
The mice received aspiration of gastric fluid on days 1, 8, 15, 22, 29, 36, 43, and 50 and were sensitized to ovalbumin by intraperitoneal (IP) injection on days 33 and 47, challenged with aerosolized ovalbumin on day 54, and killed on day 56. Control mice received sham gastric fluid aspirations, sham induction of airway hypersensitivity, or both.
Chronic aspiration of 50 μl murine gastric fluid once per week for 8 weeks had a profound effect on the immune system in the lung, with upregulation of the macrophage/monocyte-associated cytokines tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) and profound downregulation of a broad array of T-cell-associated cytokines including interleukins 2, 4, 5, 6, 10, 13, and 23, as well as interferon-γ. The aspiration-induced depression of IL-5 production in particular was found only in mice with airway hypersensitivity and not in control mice without airway hypersensitivity.
The results indicate that chronic aspiration of gastric fluid has a profound effect on the nature of the allergic response to aerosolized allergens, suggesting that the aspiration may be an important factor affecting the pathogenesis of asthma.
KeywordsAspiration Asthma Experimental model Gastroesophageal reflux
This work was supported by a Society of American Gastrointestinal Endoscopic Surgeons research grant, and in part by the Parks Protocol Memorial Fund, the American Association for Thoracic Surgery Second Dwight Harken Research Scholarship, the American College of Surgeons Faculty Research Fellowship Award, the Duke Heart Center Career Development Award, and the Fannie E. Rippel Foundation. We thank Roxanne Wilson for her technical assistance.
Anitra D. Thomas, Kuei-Ying Su, Jui-Chih Chang, Jason H. Leung, Sean M. Lee, Zoie E. Holzknecht, Mary Lou Everett, William Parker, R. Duane Davis, and Shu S. Lin have no conflicts of interest or financial ties to disclose.
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