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.
Päth
G
G
Diabetes Forschungsinstitut, Düsseldorf, Germany. paeth@post.med.uni-marburg.de
Scherbaum
W A
WA
Bornstein
S R
SR
D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000032:analysis; D013256:Steroids / Q000096:biosynthesis
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D013256:Steroids