Date of Award

Fall 2011

Degree Type

Thesis

Degree Name

Master of Science (MSc)

Department

Medical Sciences

Supervisor

Mark Larche

Co-Supervisor

Parameswaran Nair

Language

English

Committee Member

Mark Inman, Frederick Hargreave

Abstract

Asthma is a lung disease characterized by wide variations in airflow over short periods of time. Exacerbations of asthma can be accompanied by symptoms of chest tightness, shortness of breath and wheezing; airway inflammation characterized by an influx of eosinophils and/or neutrophils; and the expression of pro-inflammatory cytokines in the airway. There is strong evidence supporting a central role for the T cell in asthma. In atopic asthma, T cells are documented components of the late-phase response to inhaled allergen, driving airway inflammation, mucus hypersecretion, and bronchoconstriction through the release of cytokines and other mediators. T cells have also been shown to produce inflammatory cytokines in response to allergen in nonatopic asthmatics, indicating a potential role in mediating disease in this phenotype. In both atopic and nonatopic asthma, aberrant T cell responses to allergen may drive the infiltration of neutrophils and eosinophils into the airway through the production of pro- inflammatory cytokines, leading to exacerbations of disease. This project has investigated the role of several T cell cytokines in driving disease and acting as biomarkers in asthma: interleukin-5, interleukin-17A, interleukin-23, interleukin- 10, and interferon-γ. We have measured allergen-induced cytokine production by peripheral blood mononuclear cells (PBMCs) and examined its ability to distinguish between different asthma phenotypes: asthma vs normal, atopic vs nonatopic asthma, eosinophilic bronchitis vs noneosinophilic bronchitis, and neutrophilic vs nonneutrophilic bronchitis. Our data shows that allergen-induced peripheral blood mononuclear cell responses to allergen are not good biomarkers of disease in asthma. No differences in PBMC cytokine production are seen in patients with asthma, compared with normal controls, or between patients with different asthmatic phenotypes. It is not possible to determine a patient’s disease state, atopic status, or type of bronchitis by examining their PBMC cytokine responses to allergen.

McMaster University Library


Download

Share

COinS