Feed-back interactions between cytokines and the HPA axis

Journal/Book: Z Rheumatol 1999; 58: 297. 1999;

Abstract: H. O.Besedovsky; Institut für Normale und Pathologische Physiologie -Immunophysiologie- der Philipps-Universität Marburg Neuro-endocrine host responses are known to occur during certain infectious inflammatory autoimmmune and neoplastic processes. It is now becoming evident that these responses are not or not only triggered by the causal agent of the disease its products and/or by physical or functional alterations of the organs affected but rather by cytokines released by activated immune cells. Indeed the immune response to innocuous antigens and acute stimulation of certain immunologic cells cause the stimulation of the HPA axis. This effect can be mimicked in vitro since stimulation of immune cells using antigens and mitogens results in the release of mediators that when inoculated into naive animals cause an increase in glucocorticoids and ACTH levels. These mediators were generically termed glucocorticoid increasing factors (GIF) and the first of them to be characterized was IL-1ß. Very low doses of this cytokine cause an acute and pronounced elevation of ACTH and glucocorticoid blood levels in all animal species so far tested. This effect is totally abrogated by blocking CRH production or action showing that the cytokine directly or indirectly affect neurons of the paraventricular nucleus of the hypothalamus and therefore cause the stimulation of the HPA axis at this level. However there is evidence that a prolong production of IL-1 can also cause the stimulation of pituitary corticotrophs and adrenal cells. When administered systematicaly IL-1 does not stimulate the release of "stress hormones" such as prolactin and growth hormone and only marginally elevates the level of catecholamines in blood. Therefore the stimulation of the HPA axis by IL-1 does not reflect a massive activation of neuro-endocrine mechanisms that characterizes the acute response to stress. ... le

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