Chronic aspiration shifts the immune response from adaptive immunity to innate immunity in a murine model of asthma
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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.
Forty-eight male C57BL/6 mice were used.
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.
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.
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.
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.
KeywordsGastroesophageal reflux Aspiration Asthma Innate immunity Adaptive immunity
This work was supported by the 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 and Julie Fuller for their technical assistance.
Conflict of interest
The authors have no competing interests to declare.
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