Chronic aspiration shifts the immune response from adaptive immunity to innate immunity in a murine model of asthma

Kuei Ying Su, Anitra D. Thomas, Jui Chih Chang, Jason H. Leung, Sean M. Lee, Zoie E. Holzknecht, Mary Lou Everett, W. Michael Foster, Monica Kraft, William Parker, R. Duane Davis, Shu S. Lin

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Abstract

Objective and design: The hypothesis that aspiration of gastric fluid drives the anti-ovalbumin response toward a Th2 reaction even in animals not prone to Th2 responses was evaluated. Subjects: Forty-eight male C57BL/6 mice were used. Methods: Mice were sensitized and challenged with ovalbumin starting 5 weeks prior to the initiation of weekly aspirations of either gastric fluid or normal saline as a control. Weekly aspiration continued during the course of exposure to ovalbumin. Treatment: Aspiration consisted of 50 μl of gastric fluid with 50 μl of 0.9 % normal saline used as a control. Antigen exposure consisted of sensitization to ovalbumin via intraperitoneal injection on days 0 and 14 and challenge on day 21 with aerosolized antigen for 30 min. Results: No evidence of a shift toward a Th2 response as a result of gastric fluid aspiration was seen in the Th1-prone strain utilized, although a profound down-regulation of a broad array of T cell-associated cytokines and chemokines and up-regulation of macrophage-associated markers was observed as a result of aspiration. Conclusions: These data provide support for the hypothesis that the clinical association between asthma and gastroesophageal reflux disease (GERD) does not involve an exacerbation of asthma by GERD-associated aspiration of gastric fluid, but may cause immune reactions unrelated to the asthma pathology.

Original languageEnglish (US)
Pages (from-to)863-873
Number of pages11
JournalInflammation Research
Volume61
Issue number8
DOIs
StatePublished - Aug 1 2012

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Keywords

  • Adaptive immunity
  • Aspiration
  • Asthma
  • Gastroesophageal reflux
  • Innate immunity

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Su, K. Y., Thomas, A. D., Chang, J. C., Leung, J. H., Lee, S. M., Holzknecht, Z. E., Everett, M. L., Michael Foster, W., Kraft, M., Parker, W., Duane Davis, R., & Lin, S. S. (2012). Chronic aspiration shifts the immune response from adaptive immunity to innate immunity in a murine model of asthma. Inflammation Research, 61(8), 863-873. https://doi.org/10.1007/s00011-012-0479-x