The role of interleukin-6 in the human adrenal gland.

Interleukin (IL)-6 is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis on all levels in humans, and appears to play a pathogenic role in conditions related to chronic stress and physiological ageing; with physiological ageing showing a similar hormonal and immunological pattern to chronic stress. IL-6 and its receptor IL-6R are co-expressed at similar sites in the human adrenal gland, which seems to be an important source of IL-6 production. In vitro, in primary cultures of adrenal gland cells, chronic exposure to IL-6 stimulates adrenocortical steroid release in a time- and dose-dependent manner. This explains the high systemic cortisol levels in the absence of adequate plasma concentrations of corticotropin (ACTH) observed in patients after long-term treatment with IL-6. It could therefore be concluded that in situations of prolonged stress, when corticotropin-releasing hormone and ACTH release are suppressed by feedback inhibition due to circulating glucocorticoids, IL-6 maintains the elevated glucocorticoid levels by direct stimulation of adrenocortical steroidogenesis via autocrine/paracrine mechanisms.