Neuroendocrine regulation of air pollution health effects: Emerging insights

Abstract

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 lungmight induce effects in distant organs. The role of circulatingmediators 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 inmediating a wide array of systemic and pulmonary effects. Our recent studies using ozone exposure as a prototypical air pollutant demonstrate that increases in circulating adrenalderived stress hormones (epinephrine and cortisol/corticosterone) contribute to lung injury/inflammation andmetabolic effects in the liver, pancreas, adipose, andmuscle 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 systemis critical for normal homeostasis and allostatic activation; however, chronic exposure to stressorsmay lead to increases in allostatic load. The emergingmechanisms by which circulatingmediators are released and are responsible for producingmultiorgan effects of air pollutants insists upon a paradigmshift 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.