title: Gastroesophageal reflux-associated aspiration alters the immune response in asthma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Chronic aspiration of 50 microl 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-alpha (TNF-alpha) 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-gamma. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Duke University Medical Center, DUMC Box 2605, Durham, NC 27710, USA.
authors.forename: Anitra D
authors.initials: AD
authors.lastname: Thomas
authors.forename: Kuei-Ying
authors.initials: KY
authors.lastname: Su
authors.forename: Jui-Chih
authors.initials: JC
authors.lastname: Chang
authors.forename: Jason H
authors.initials: JH
authors.lastname: Leung
authors.forename: Sean M
authors.initials: SM
authors.lastname: Lee
authors.forename: Zoie E
authors.initials: ZE
authors.lastname: Holzknecht
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Everett
authors.forename: William
authors.initials: W
authors.lastname: Parker
authors.forename: R Duane
authors.initials: RD
authors.lastname: Davis
authors.forename: Shu S
authors.initials: SS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D005744:Gastric Acid / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000378:metabolism; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12