title: Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response.
abstract: Inhaled pollutants produce effects in virtually all organ systems in our body and have been linked to chronic diseases including hypertension, atherosclerosis, Alzheimer's and diabetes. A neurohormonal stress response (referred to here as a systemic response produced by activation of the sympathetic nervous system and hypothalamus-pituitary-adrenal (HPA)-axis) has been implicated in a variety of psychological and physical stresses, which involves immune and metabolic homeostatic mechanisms affecting all organs in the body. In this review, we provide new evidence for the involvement of this well-characterized neurohormonal stress response in mediating systemic and pulmonary effects of a prototypic air pollutant - ozone. A plethora of systemic metabolic and immune effects are induced in animals exposed to inhaled pollutants, which could result from increased circulating stress hormones. The release of adrenal-derived stress hormones in response to ozone exposure not only mediates systemic immune and metabolic responses, but by doing so, also modulates pulmonary injury and inflammation. With recurring pollutant exposures, these effects can contribute to multi-organ chronic conditions associated with air pollution. This review will cover, 1) the potential mechanisms by which air pollutants can initiate the relay of signals from respiratory tract to brain through trigeminal and vagus nerves, and activate stress responsive regions including hypothalamus; and 2) the contribution of sympathetic and HPA-axis activation in mediating systemic homeostatic metabolic and immune effects of ozone in various organs. The potential contribution of chronic environmental stress in cardiovascular, neurological, reproductive and metabolic diseases, and the knowledge gaps are also discussed. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: kodavanti.urmila@epa.gov.
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D019570:Inhalation Exposure; D010126:Ozone / Q000633:toxicity*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*; D013312:Stress, Physiological
chemical_list: D000393:Air Pollutants; D006728:Hormones; D010126:Ozone
keywords: Air pollution; Inflammation; Metabolism; Stress hormones; Stress response