Schöbitz B, Holsboer F, Sutanto W, Gross G, Schönbaum E, de Kloet E R
Leiden-Amsterdam Institute for Drug Research, Division of Medical Pharmacology, Leiden University, The Netherlands.
Neuroendocrinology. 1994 Apr;59(4):387-95. doi: 10.1159/000126682.
The role of endogenous corticoids in fever responses caused by recombinant murine interleukin (IL)-1 beta and IL-6 was studied in adult male Wistar rats. Adrenalectomy diminished the development of fever after intracerebroventricular (icv) injection of these ILs and lowered body temperature. Intraperitoneal administration of the same doses of ILs did not produce fever in intact animals or hypothermia in adrenalectomized rats, thus suggesting a central site of action of IL-1 beta and IL-6 in these experiments. Chronic replacement with moderate doses of corticosterone restored the fever response in adrenalectomized animals in response to icv administration of IL-1 beta but only partially reversed the fever caused by IL-6. Adrenalectomized animals acutely treated with corticosterone and thereafter with either IL-1 beta or IL-6 developed fever more rapidly than did chronically corticosterone-treated animals. In intact animals corticosterone blocked the fever response to icv injected IL-1 beta. We propose that in the rat corticosterone acts in a bimodal manner on body temperature; it exerts a permissive central effect on the fever response and limits the production of inflammatory mediators in the brain. Conversely, higher corticosterone doses probably reduce the magnitude of the fever response.
在成年雄性Wistar大鼠中研究了内源性皮质激素在重组鼠白细胞介素（IL）-1β和IL-6引起的发热反应中的作用。肾上腺切除减弱了脑室内（icv）注射这些白细胞介素后发热的发展并降低了体温。腹腔注射相同剂量的白细胞介素在完整动物中不产生发热，在肾上腺切除的大鼠中也不产生体温过低，因此表明在这些实验中IL-1β和IL-6的作用部位在中枢。用中等剂量的皮质酮进行慢性替代可恢复肾上腺切除动物对icv注射IL-1β的发热反应，但仅部分逆转IL-6引起的发热。用皮质酮急性处理后再用IL-1β或IL-6处理的肾上腺切除动物比长期用皮质酮处理的动物发热更快。在完整动物中，皮质酮阻断了对icv注射IL-1β的发热反应。我们提出，在大鼠中皮质酮对体温有双峰作用；它对发热反应发挥允许性的中枢作用，并限制脑中炎症介质的产生。相反，较高剂量的皮质酮可能会降低发热反应的程度。
