Regulation of the hypothalamo–pituitary–adrenal axis by cytokines

Many of the pro-inflammatory cytokines which are released in response to immune/inflammatory insults exert marked stimulatory influences on the hypothalamo–pituitary–adrenocortical (HPA) axis; they thus provoke the release of glucocorticoids which, in turn, temper the ensuing immune–inflammatory response and thereby complete a homeostatic neuroendocrine–immune regulatory loop. This article reviews the putative mechanisms by which cytokines, released acutely in response to such insults, activate the HPA axis, placing particular emphasis on the actions and interactions of tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) and on the counter-regulatory mechanisms that are in place.