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Title: Obesity and asthma : the role of innate immunity, adipokines and regulatory T cells
Author: Pynn, Michael
ISNI:       0000 0004 7425 4652
Awarding Body: Swansea University
Current Institution: Swansea University
Date of Award: 2014
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Introduction: Obesity and asthma are associated but the mechanism is poorly understood. Enhanced systemic inflammation may underlie the obesity-asthma paradigm. Although there is good mechanistic data that obesity augments the immune response as well as promoting immune dysregulation by reducing regulatory T cell numbers, there is little work relating this to obesity and asthma. Methods: A case-control study examined 6 groups of pre-menopausal women (n=84); non-obese, f overweight and obese individuals with and without asthma. Measures of adiposity and lung function I were taken and peripheral blood collected during the first 7 days of the menstrual cycle. Innate immune parameters measured included: full blood count and differential; chemiluminescence recorded whole blood reactive oxygen species; neutrophil related cytokines; neutrophil and i monocyte activation markers by flow cytometry, and LPS induced whole blood cytokine responses. Insulin resistance, adipokine levels and free fatty acid levels were recorded. Dendritic cell and lymphocyte subtypes including FoxP33+ regulatory T cells (Tregs) were quantified by flow cytometry I and PHA-induced cytokine responses measured in whole blood. Results: Obesity and asthma appeared to have synergistic effects with regards to circulating I neutrophil count, plasma IL-6 and leptin with obese asthmatics having the highest levels. Reactive I oxygen species production followed a similar trend. Increasing BMI within asthmatics was associated f with a reduction in eosinophils and myeloid dendritic cells, and increased PHA-induced IFNy. Obesity I across the entire study group was associated with increased neutrophil counts and neutrophil P related cytokines, reduced FoxPS3+Tregs and increased PHA-induced IL-17 response. Conclusions: Systemic changes in immunity occur in obesity and asthma; some of these are additive. Within asthmatics, obesity is associated with responses suggesting T helper 1 (Th1) rather than Th2 bias. Obesity-associated systemic changes in immunity might encourage a loss of immune tolerance. These findings suggest that obesity might mediate its effects in asthma through systemic inflammatory mechanisms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available