Abstract
Exposure to psychosocial stress has been associated with increasing rates of morbidity in humans and in animal models, but the underlying mechanisms are not completely understood. Major stress responsive systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system (ANS) are under investigation as underlying pathways, but although acute stress reliably activates these systems, findings of long-term alternations in baseline activity are inconsistent at present. Emerging evidence suggests that stress-related changes in the sensitivity of target systems toward glucocorticoid (GC) regulation, i.e. development of GC resistance, might help explain inflammatory disinhibition and development of disease related to inflammation. More recent findings further show that the autonomic nervous system might play an important role in the regulatory control of the inflammatory cascade. The major argument put forward in this manuscript is that target tissues for stress system modulation, such as the inflammatory cascade, vary in their ability to respond to stress system signaling, and that assessing alterations in this stress signal sensitivity which can be caused by stress or disease processes, might be necessary to understand and explain stress effects on health. This review focuses on the inflammatory system in particular, because anti-inflammatory effects of most stress systems have been documented, but the general assumption might have to be generalized to other target systems. The main conclusion to be made is that reduction in glucocorticoid sensitivity of target tissues is the most consistent finding at present, and that assessing such changes in glucocorticoid sensitivity might be necessary to understand many stress-related changes in physiology.
