Central effects of glucocorticoid receptor antagonist RU-38486 on lipopolysaccharide and stress-induced fever.
Central effects of glucocorticoid receptor antagonist RU-38486 on lipopolysaccharide and stress-induced fever.
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糖皮质激素受体拮抗剂 RU-38486 对脂多糖和应激性发热的中枢作用。
DOI：
10.1152/ajpregu.1994.267.3.r705
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Kluger,MJ
中科院分区：
文献类型：
--
作者：
McClellan,JL;Klir,JJ;Morrow,LE;Kluger,MJ
脑室内给予糖皮质激素II型受体拮抗剂RU-38486可导致清醒无约束大鼠注射脂多糖（LPS）后发热升高，表明内源性糖皮质激素在腹腔注射LPS后起到降低体温的中枢作用。目前的研究检查了大脑中糖皮质激素对发烧的影响，以及这些影响是否涉及血浆白细胞介素-6和皮质酮。与对照组相比，脑室内注射RU-38486 （10 ng/ml）导致lps （50 mg/kg ip）后120-240 min生物遥测体温（BT）显著升高（0.89 +/- 0.14 vs. 0.44 +/- 0.22℃，P = 0.0482），证实了我们早期的研究，并且当脑室内注射RU-38486 （10 ng/ml）时，暴露于开放区域后BT也显著升高。1微升/小时)，暴露前20小时（1.48 +/- 0.18 vs. 1.06 +/- 0.11℃，P = 0.023）。当大鼠下丘脑前部注射RU-38486 （1 ng/只）时，注射LPS后BT升高（1.74 +/- 0.27 vs. 0.82 +/- 0.22℃，P = 0.0075），但暴露于开放区域（1 ng下丘脑内，暴露前1 h）后BT升高不明显。脑室内注射RU-38486与腹腔注射LPS后，血浆白细胞介素-6样活性和血浆皮质酮均无差异。我们得出结论，内源性糖皮质激素在LPS和暴露于开阔场地后的发热中起中枢调节作用，LPS诱导的发热是由下丘脑前部的糖皮质激素调节的。（摘要删节250字）
Intracerebroventricular administration of the glucocorticoid type II receptor antagonist RU-38486 leads to an increased fever after injection of lipopolysaccharide (LPS) in awake unrestrained rats, indicating that endogenous glucocorticoids act centrally to lower temperature after the intraperitoneal injection of LPS. The current study examined where in the brain glucocorticoids exert these effects on fever and if these effects involve plasma interleukin-6 and corticosterone. RU-38486 injected intracerebroventricularly (10 ng/animal) led to a significantly greater rise in biotelemetered body temperature (BT) 120-240 min post-LPS (50 mg/kg ip) compared with controls (0.89 +/- 0.14 vs. 0.44 +/- 0.22 degree C, P = 0.0482), confirming our earlier study, and also led to a significantly greater rise in BT after exposure to an open field when the RU-38486 was infused intracerebroventricularly (10 ng/ml, 1 microliter/h) for 20 h before the exposure (1.48 +/- 0.18 vs. 1.06 +/- 0.11 degree C, P = 0.023). When rats were injected with RU-38486 into the anterior hypothalamus (1 ng/animal), there was an increased rise in BT after injection of LPS (1.74 +/- 0.27 vs. 0.82 +/- 0.22 degree C, P = 0.0075) but not after exposure to an open field (1 ng intrahypothalamically, 1 h preexposure). There were no differences in plasma interleukin (IL)-6-like activity or plasma corticosterone after intracerebroventricular injection of RU-38486 and intraperitoneal injection of LPS. We conclude that endogenous glucocorticoids are working centrally to modulate fever after LPS and exposure to open field, and that LPS-induced fever is modulated by glucocorticoids in the anterior hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)