Chronic aspiration shifts the immune response from adaptive immunity to innate immunity in a murine model of asthma.
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.
Su, K-Y; Thomas, AD; Chang, J-C; Leung, JH; Lee, SM; Holzknecht, ZE; Everett, ML; Foster, WM; Kraft, M; Parker, W; Davis, RD; Lin, SS
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