Variability in stress system regulatory control of inflammation: a critical factor mediating health effects of stress

Chronic stress has been associated with disease but the biological pathways are not completely understood. Stress systems such as the hypothalamus-pituitary-adrenal axis and the autonomic nervous system are prime candidates but alterations in their baseline activity are not consistently found in chronic stress. Evidence suggests that stress-related changes in the sensitivity of inflammatory pathways towards glucocorticoid regulation, that is, the development of glucocorticoid resistance, might help explain inflammatory disinhibition and the subsequent development of disease. Recent data show a similarly important role for sympathetic and parasympathetic modulation of the inflammatory cascade for the maintenance of health. This article argues that variation of target tissue sensitivity towards anti-inflammatory effects of the hypothalamus-pituitary-adrenal axis, as well as sympathetic and parasympathetic signaling, might be involved in the development of low-grade inflammation under chronic psychosocial stress.