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Published ahead of print on July 19, 2007, doi:10.1164/rccm.200702-323OC

Am. J. Respir. Crit. Care Med., Volume 176, Number 7, October 2007, 650-658

A more recent version of this article appeared on October 1, 2007
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Submitted on February 26, 2007
Accepted on July 19, 2007

Allergic Airway Responses in Obese Mice

Richard A Johnston1*, Ming Zhu1, Yadira M Rivera-Sanchez1, Frank L Lu2, Todd A Theman1, Lesley Flynt1, and Stephanie A Shore1

1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA, 2 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA; Department of Pediatrics, National Taiwan University Hospital and Medical College, National Taiwan University, Taipei, Taiwan

* To whom correspondence should be addressed. E-mail: rajohnst{at}utmb.edu.

Rationale: Epidemiological data indicate an increased incidence of asthma in the obese. Objective: To determine whether obese mice exhibit augmented pulmonary responses following allergen sensitization and challenge. Methods: Lean, wildtype (C57BL/6), obese ob/ob, and obese db/db mice were sensitized to ovalbumin (OVA), and then challenged with aerosolized OVA or phosphate-buffered saline (PBS). Changes in total pulmonary resistance (RL) induced by intravenous methacholine were measured by forced oscillation. Blood was collected, bronchoalveolar lavage (BAL) was performed, and lungs were harvested for measurement of cytokine expression by real-time RTPCR. Measurements and Main Results: OVA challenge increased baseline RL in ob/ob, but not wildtype mice, and airway responsiveness was greater in ob/ob than wildtype mice, regardless of the challenge. Compared to PBS, OVA challenge caused an increase in the number of BAL fluid (BALF) cells, an increase in lung Th2 cytokine expression, and an increase in serum immunoglobulin E (IgE). Significantly fewer BALF cells were recovered from OVA-challenged ob/ob versus wildtype mice, while serum IgE levels were elevated significantly more in ob/ob versus wildtype mice. BALF and lung Th2 cytokine expression were not different in ob/ob versus wildtype mice. Airway responsiveness was greater in db/db versus wildtype mice, regardless of the challenge, and OVA caused airway hyperresponsiveness in db/db but not wildtype mice, despite reduced BALF cells in OVA challenged db/db versus wildtype mice. Conclusions: These results demonstrate that obesity enhances OVA-induced changes in pulmonary resistance and serum IgE and that these changes are not the result of increased Th2 type airway inflammation.


Key words: airway responsiveness, eosinophil, immunoglobulin E, interleukin-13, pulmonary resistance




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