UBC Theses and Dissertations
Adipokine responses in the lung and circulation in atopic adults upon exposure to allergen and diesel exhaust Kramer, Marabeth
Introduction: Adipokines are inflammatory mediators released primarily from the adipose tissue. These proteins are now recognized as active elements of systemic and pulmonary inflammatory responses, whose dysregulation can prime the development of allergic lung diseases. The purpose of this study was to measure adipokine responses in an atopic adult study population following exposure to allergen and diesel exhaust. Characterizing adipokine responses in the lung and in the serum, in an atopic but otherwise healthy population, can provide insight into adipokine responses in sensitized to specific allergens, yet without co-morbidities. Methods: Lung and blood samples were collected from subjects participating in a randomized, double-blinded controlled human study with crossover to two conditions: inhaled diesel exhaust and inhaled filtered air, each of which were followed by lung-instilled allergen (and contralateral saline control). Serum samples collected at baseline, 4, 24 and 48 hours after allergen instillation, and lung samples collected at 48 hours after allergen were assayed for total adiponectin, leptin and resistin using ELISA. Mixed-effects models were used for statistical analysis to determine exposure effect, and effect modification by sex, BMI status and airway responsiveness. Results: Adiponectin and leptin were significantly increased in the lung in response to allergen. Leptin and resistin changed in the serum in a diurnal pattern, but levels were not altered by diesel exhaust. Diesel exhaust and allergen co-exposure significantly increased the adiponectin/leptin ratio in the lung relative to allergen alone, in subjects with normal airway responsiveness. Conclusion: Increases in lung adipokines in response to allergen exposure were identified in the context of a controlled human exposure study. Some effect modification by sex, BMI and airway responsiveness occurred. Diesel exhaust along with allergen induced a protective adipokine pattern in the lung in those with normal airway responsiveness. The clinical relevance and generalizability of these findings, herein noted in atopic individuals, warrants further study.
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