Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model of asthma
Version of Record online: 17 JUL 2008
© 2008 The Authors. Journal Compilation © 2008 Blackwell Publishing Ltd
European Journal of Clinical Investigation
Volume 38, Issue 8, pages 596–602, August 2008
How to Cite
Barbas, A. S., Downing, T. E., Balsara, K. R., Tan, H. E., Rubinstein, G. J., Holzknecht, Z. E., Collins, B. H., Parker, W., Davis, R. D. and Lin, S. S. (2008), Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model of asthma. European Journal of Clinical Investigation, 38: 596–602. doi: 10.1111/j.1365-2362.2008.01976.x
- Issue online: 17 JUL 2008
- Version of Record online: 17 JUL 2008
- Received 20 December 2007; accepted 24 April 2008
- airway hypersensitivity;
- chronic aspiration;
- gastro oesophageal reflux;
Background Chronic aspiration associated with gastro oesophageal 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.
Materials and methods Four experimental groups were utilized: Aspiration/Asthma, Sham/Asthma, Aspiration/Sham and Sham/Sham. Mice were sensitized with aerosolized 1% ovalbumin on days 1 to 10 (sensitization phase), followed by repeated exposure on days 31 to 40 (challenge phase). Aspiration events occurred on days 1, 8,15, 22, 29, 36, 43 and 50. Animals were sacrificed on days 56 and 57.
Results Chronic aspiration of 10 µL 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 antiovalbumin IgG, antiovalbumin IgE, and total IgE. Further, aspiration induced a substantial and significant increase in antiovalbumin IgG1/IgG2a ratios, consistent with a shift toward a predominantly Th2 response.
Conclusion 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.