Activation of the hypothalamus-pituitary-adrenal axis by cytokines

Activation of the hypothalamus-pituitary-adrenal axis is among the endocrine changes that occur during the acute-phase response to infection or inflammation. These responses have been ascribed to the release of endogenous cytokines. In the present paper a number of studies on effects of interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6) and tumour necrosis factor on the hypothalamus-pituitary-adrenal axis are discussed. In addition some recent data from our laboratory on acute and chronic administration of cytokines are presented. Our data show that continuous infusion of rats with IL-1 elicits a long-term activation of adrenal corticosterone (B) production, suggesting that this peptide is a mediator of the effect of infection or inflammation on the activity of the hypothalamus-pituitary-adrenal axis. Although there is still controversy concerning the site of action of cytokines on the hypothalamus-pituitary-adrenal axis, there is consensus that acutely administered IL-1 increases plasma ACTH and corticosterone levels through activation of hypothalamic CRH neurons. On the other hand, it is possible that during prolonged treatment IL-1 activates the hypothalamus-pituitary-adrenal axis via a rapid effect on hypothalamic CRH neurons and via a delayed effect which results from a direct stimulation of pituitary and/or adrenal cells.