Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis.

Abstract

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by the cells of immune and nonimmune origin. Increased production of IL-6 is associated with disturbances of homeostasis, such as trauma, sepsis, or inflammatory diseases. Endotoxemia, tissue injury, or immune inflammatory reactions as well as physical or psychological stress are known to cause increased production of IL-6. We have confirmed this by showing that rats exposed to electric footshock, physical restraint, or a conditioned aversive stimulus have increased levels of plasma IL-6. Interestingly, the kinetics of the increase in plasma IL-6 resembled that of increase in plasma corticosterone. As no detectable endotoxin was found in the plasma samples from stressed and nonstressed rats and there is no evidence of tissue damage and inflammation in situations of restraint or conditioned aversive stimulus, a nonimmune origin of IL-6 is possible. Thus, the releasing of IL-6 into plasma may be under the regulation of neural and endocrine responses to stress. This hypothesis is supported by the decreased production of IL-6 in cultures of splenic cells and peripheral blood mononuclear cells from stressed animals. Furthermore, substantial attenuation of increased plasma IL-6 was achieved by adrenalectomy but not by pretreatment with the beta-receptor antagonist propranolol. The important role of the adrenal gland in the IL-6 response to stress suggests that increased plasma IL-6 may be part of the hormonal responses to stress. As IL-6 induces acute-phase proteins along with glucocorticoids from the adrenal, and regulates the secretion of various hormones from neuroendocrine and endocrine tissues, it is possible that stress-induced increase in plasma IL-6 contributes to the maintenance of homeostasis.

Expression of miR‐18a and miR‐34c in circulating monocytes associated with vulnerability to type 2 diabetes mellitus and insulin resistance

“…Many studies revealed that various psychological stressors alone can induce proinflammatory (IL‐1, IL‐6, TNF‐α) 15, 16, yet the mechanism and target cell for such cytokine production are not known for certain.…”

Associations Between Dimensions of Job Stress and Biomarkers of Inflammation and Infection

“…It is believed that psychosocial stress induces neuroendocrine stress responses by stimulation of the hypothalamic-pituitaryadrenal (HPA) axis and thus increases circulating levels of IL-6, which in turn is an important regulator of CRP. 29,44,45 It is hypothesized that the relation between stress and CVD may partly be mediated by an increased susceptibility to infectious disease, although the predictive value of infectious biomarkers regarding coronary heart disease is uncertain. 46 For a long time, it has been suggested that psychologic distress may be associated with the onset of infectious diseases.…”

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

“…This reduced GR response was related to high serum TNF-a and IL-6 levels. Since psychological or physical stress was shown to result in an enhanced IL-6 secretion in the peripheral immune system, [149][150][151] the functional relationship between cytokines and HPA axis activity is of pivotal interest in MD research. Psychological stress not only directly induce the activity of the HPA axis, but may also induce it indirectly through increased IL-6 levels.…”