Cytokines and the hypothalamic-pituitary-adrenal axis.

After administration of the cytokines interleukin 1 (IL1), tumor necrosis factor (TNF), interleukin 2 and interleukin 6 to laboratory animals or humans, plasma levels of glucocorticoids are elevated. This effect is mediated by activation of the hypothalamic-pituitary unit. IL1 and TNF inhibit aldosterone production by rat adrenocortical cells in vitro and stimulate renin release by rat renal cortical cells. Administration of IL1 or TNF in rats suppresses hypothalamic-pituitary-thyroid function, whereas IL1 acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. During stimulation of the immune system (e.g. during infectious diseases), peculiar alterations in hormone secretion occur (hypercortisolism, hyperreninemic hypoaldosteronism, euthyroid sick syndrome, hypogonadism). The role of cytokines in these alterations remains to be established.