Neuroendocrine Regulation of Air Pollution Health Effects: Emerging Insights.

Air pollutant exposures are linked to cardiopulmonary diseases, diabetes, metabolic syndrome, neurobehavioral conditions, and reproductive abnormalities. Significant effort is invested in understanding how pollutants encountered by the lung might induce effects in distant organs. The role of circulating mediators has been predicted; however, their origin and identity have not been confirmed. New evidence has emerged which implicates the role of neuroendocrine sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenal (HPA) stress axes in mediating a wide array of systemic and pulmonary effects. Our recent studies using ozone exposure as a prototypical air pollutant demonstrate that increases in circulating adrenal-derived stress hormones (epinephrine and cortisol/corticosterone) contribute to lung injury/inflammation and metabolic effects in the liver, pancreas, adipose, and muscle tissues. When stress hormones are depleted by adrenalectomy in rats, most ozone effects including lung injury/inflammation are diminished. Animals treated with antagonists for adrenergic and glucocorticoid receptors show inhibition of the pulmonary and systemic effects of ozone, whereas treatment with agonists restore and exacerbate the ozone-induced injury/inflammation phenotype, implying the role of neuroendocrine activation. The neuroendocrine system is critical for normal homeostasis and allostatic activation; however, chronic exposure to stressors may lead to increases in allostatic load. The emerging mechanisms by which circulating mediators are released and are responsible for producing multiorgan effects of air pollutants insists upon a paradigm shift in the field of air pollution and health. Moreover, since these neuroendocrine responses are linked to both chemical and nonchemical stressors, the interactive influence of air pollutants, lifestyle, and environmental factors requires further study.