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Allergic Airway Responses in Obese Mice

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

Correspondence and requests for reprints should be addressed to Richard A. Johnston, Ph.D., Room 8.104A, Medical Research Building, Division of Allergy, Pulmonary, Immunology, Critical Care, and Sleep, Department of Internal Medicine, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1083. E-mail: rajohnst{at}utmb.edu

Rationale: Epidemiologic data indicate an increased incidence of asthma in the obese.

Objectives: To determine whether obese mice exhibit augmented pulmonary responses after allergen sensitization and challenge.

Methods: Lean, wild-type (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 reverse transcription–polymerase chain reaction.

Measurements and Main Results: OVA challenge increased baseline RL in ob/ob, but not wild-type, mice, and airway responsiveness was greater in ob/ob than wild-type mice, regardless of the challenge. Compared with 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 IgE. Significantly fewer BALF cells were recovered from OVA-challenged ob/ob versus wild-type mice, whereas serum IgE levels were elevated significantly more in ob/ob versus wild-type mice. BALF and lung Th2 cytokine expression was not different in ob/ob versus wild-type mice. Airway responsiveness was greater in db/db versus wild-type mice, regardless of the challenge, and OVA caused airway hyperresponsiveness in db/db but not wild-type mice, despite reduced BALF cells in OVA-challenged db/db versus wild-type 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

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Obesity is a risk factor for the development of asthma. However, the mechanistic basis for this relationship is not known. What This Study Adds to the Field Obese mice exhibit enhanced airway responsiveness to methacholine and augmented IgE production and/or release following allergen sensitization and challenge.

 

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