Peripheral Blood Mononuclear Cells, Exercise, and Children: Initial Mechanisms

University Of California-Irvine, Irvine CA

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Abstract

An alarming increase in the prevalence of childhood asthma has been observed in the past several decades[unreadable] and is likely the result of an interaction among poorly understood immune, environmental, and genetic[unreadable] factors. Exercise is a common cause of asthma exacerbation in children, and it is now known that when[unreadable] children exercise, even healthy children engaged in real-life activities, a robust stress/inflammatory response[unreadable] ensues leading to activation of immune cells and cytokines, many of which are known to be involved in the[unreadable] pathogenesis of asthma. A seemingly paradoxical response to exercise occurs characterized by[unreadable] simultaneous and vigorous pro- and anti-inflammatory activation. Whether or not the naturally occurring[unreadable] leukocyte stress/inflammatory response to exercise is imbalanced in pediatric asthma and contributes to[unreadable] exercise-induced bronchoconstriction (EIB) has not been investigated in children. The goal of this Project is[unreadable] to test a series of hypotheses focused on novel mechanisms that link exercise with asthma pathogenesis in[unreadable] children. Specifically, the aims are:[unreadable] To systematically measure in children and adolescents with mild persistent asthma the effects of brief[unreadable] bouts of exercise on leukocyte production of key cytokines and growth factors that determine TH1, TH2,[unreadable] and T-regulatory balance.[unreadable] To measure the relationship between the leukocyte response to exercise and the magnitude of EIB in[unreadable] children and adolescents with asthma.[unreadable] To determine in children and adolescents with asthma how the acute leukocyte responses to exercise are[unreadable] altered by fitness, habitual physical activity, body composition, and gender and maturational status.[unreadable] The research relies on state-of-the-art techniques to assess gene regulation in leukocytes including:[unreadable] microarray, RT-PCR, flow cytometry for surface and intracellular expression of key cytokines, and growth[unreadable] factors. A series of in-vitro cell culture experiments have been designed to determine whether leukocytes[unreadable] in children with asthma differ in their responses to exercise than in healthy controls; or, alternatively, whether[unreadable] the mechanism is found in factors within the circulation (e.g., mediators such as growth hormone, insulin-like[unreadable] growth factor-l and its binding proteins, interleukin-6, and heat shock proteins- mediators that are altered by[unreadable] exercise and are known to influence stress and immune responses. Exercise will consist of cycle ergometry[unreadable] with gas exchange measured breath by breath. Habitual physical activity will be measured with[unreadable] accelerometry, and body composition with DEXA. Lung function will be measured by spirometry before and[unreadable] after exercise.[unreadable] Lay Summary. Asthma is the major chronic disease of childhood, and exercise and play are, unfortunately,[unreadable] key triggers of asthma attacks. This research is designed to better understand how immune cells respond to[unreadable] exercise in asthma. This knowledge will help develop strategies to limit asthma attacks permitting affected[unreadable] children to prevent chronic lung disease and fully accrue the many health benefits of exercise during growth.