Abstract
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.