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Chronic Aspiration Shifts the Immunue Response from Th-1 to Th-2 in a Murine Model of Asthma

Chronic aspiration associated with gastroesophageal reflux disease (GERD) is thought to play a substantial role in the development of asthma, the incidence of which is dramatically increasing in industrially developed countries. The majority of data examining the association between aspiration and asthma has been obtained from epidemiological studies, which show that between 50 and 90% of individuals with asthma experience some element of GERD. This study describes the effect of chronic aspiration on a model of experimentally induced airway hypersensitivity in Balb/c mice.
Chronic aspiration of 10 uL of murine gastric fluid per week for eight weeks produced an injury pattern distinct from that of acute aspiration, with lung injury characterized by hyperplasia, neutrophil infiltration of the bronchioles and relative parenchymal sparing. Aspiration during induction of ovalbumin-induced airway hypersensitivity was associated with a trend toward decreased production of anti-ovalbumin IgG, anti-ovalbumin IgE, and total IgE. Further, aspiration induced a substantial and significant increase in anti-ovalbumin IgG1/IgG2a ratios, consistent with a shift toward a predominantly Th2 response. These findings indicate that chronic aspiration has a profound effect on the nature of the immune response to aerosolized allergens in a model of experimentally induced airway hypersensitivity.


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Program Number: P075

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