Susceptibility Variations in Air Pollution Health Effects: Incorporating Neuroendocrine Activation

Diverse host factors/phenotypes may exacerbate or diminish biological responses induced by air pollutant exposure. We lack an understanding of biological indicators of environmental exposures that culminate in a physiological response versus those that lead to adversity. Variations in response phenotype might arise centrally and/or at the local tissue level. In addition to genetic differences, the current evidence supports the roles of preexisting cardiopulmonary diseases, diabetes, diet, adverse prenatal environments, neurobehavioral disorders, childhood infections, microbiome, sex, and psychosocial stressors in modifying the susceptibility to air pollutant exposures. Animal models of human diseases, obesity, nutritional inadequacies, and neurobehavioral conditions have been compared with healthy controls to understand the causes of variations in susceptibility. Although psychosocial stressors have been associated with increased susceptibility to air pollutant effects, the contribution of neuroendocrine stress pathways in mediating these effects is just emerging. The new findings of neuroendocrine activation leading to systemic metabolic and immunological effects of air pollutants, and the potential contribution to allostatic load, emphasize the consideration of these mechanisms into susceptibility. Variations in susceptibility to air pollution health effects are likely to underlie host genetic and physiological conditions in concert with disrupted neuroendocrine circuitry that alters physiological stability under the influence of stressors.