Allergic airway responses in obese mice.
BACKGROUND
Epidemiologic data indicate an increased incidence of asthma in the obese.


OBJECTIVE
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.


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.
Johnston
Richard A
RA
Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA. rajohnst@utmb.edu
Zhu
Ming
M
Rivera-Sanchez
Yadira M
YM
Lu
Frank L
FL
Theman
Todd A
TA
Flynt
Lesley
L
Shore
Stephanie A
SA
D000403:Airway Resistance; D000818:Animals; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016085:Bronchoconstrictor Agents; D016207:Cytokines / Q000378:metabolism; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000473:pathology; D016210:Methacholine Chloride; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D010047:Ovalbumin; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018418:Th2 Cells / Q000473:pathology
D016085:Bronchoconstrictor Agents; D016207:Cytokines; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin