Interleukins-1 and -6 Stimulate the Release of Corticotropin-Releasing Hormone-41 from Rat Hypothalamusin Vitrovia the Eicosanoid Cyclooxygenase Pathway*

作者：Pierluigi Navarra, Stylianos Tsagarakis, Manuel dos Santos Faria, LESLEY H. REES, G. M. Besser, Ashley Barry Grossman · 发表于：Endocrinology · 年份：1991 · DOI：10.1210/endo-128-1-37 · 被引用次数：334 · 研究领域：Stress Responses and Cortisol、Adrenal Hormones and Disorders、Tryptophan and brain disorders

It has previously been shown that interleukin-1 (IL-1) directly stimulates the release of CRH-41 from rat hypothalamus in vitro, suggesting that cytokines may mediate the effects of changes in immune state on the hypothalamo-pituitary adrenal axis (HPA). However, it is likely that several cytokines can cause changes in neuroendocrine function, and we have now investigated a series of others for central activity on the HPA: IL-2, IL-6, IL-8, tumor necrosis factor (cachectin), interferon-alpha 2, and interferon-gamma. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubation, and estimation of CRH-41 concentrations in the medium by a specific RIA; the acute effects of cytokines on ACTH release from rat dispersed pituitary cells were also measured. IL-6 increased hypothalamic CRH-41 secretion in the range 10-100 U/ml, but had no effect on isolated median eminences incubated in vitro under the same conditions. IL-6 (1-1000 U/ml) also had no effect on the secretion of ACTH from freshly dispersed rat anterior pituitary cells when administered in 10-min pulses. The effects of both IL-1 and IL-6 were antagonized by blockade of the eicosanoid cyclooxygenase pathway, but not by lipooxygenase blockade. Neither IL-2 (1-10000 U/ml), IL-8 (0.1-10 nM), tumor necrosis factor (10-1000 U/ml), interferon-alpha 2 (10-1000 U/ml) nor interferon-gamma (10-1000 U/ml) had any effect on hypothalamic CRH-41 release or pituitary ACTH relea...