Endotoxin-induced corticotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is mediated centrally by interleukin-1.
Endotoxin-induced corticotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is mediated centrally by interleukin-1.
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DOI：
10.1210/endo.133.2.8344218
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发表时间：
1993-08
期刊：
影响因子：
4.8
通讯作者：
I. Kakucska;Yanping Qi;B. D. Clark;R. Lechan
中科院分区：
文献类型：
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作者：
I. Kakucska;Yanping Qi;B. D. Clark;R. Lechan
在细菌感染的急性期，外周和中枢神经系统中的细菌内毒素可诱导多种细胞因子，包括白细胞介素-1（IL-1）。先前已报道细菌内毒素深刻地激活下丘脑-垂体-肾上腺轴，导致糖皮质激素分泌升高，这可能作为对激活的免疫系统的抑制性反馈机制的一部分起重要作用。为了确定IL-1是否在脑内介导下丘脑室旁核（PVN）中内毒素诱导的CRH基因表达，我们研究了将人IL-1受体拮抗剂（IL-1 ra）（IL-1的竞争性抑制剂）注入脑内对全身性脂多糖（LPS）治疗后PVN中CRH基因表达的影响。腹腔注射LPS后8小时，室旁CRH mRNA含量升高3- 4倍（与对照组相比P 0.05）。相反，全身IL-1 ra给药不能抑制PVN内毒素诱导的CRH基因表达。这些研究表明，LPS刺激下丘脑CRH的机制，涉及在中枢神经系统内的IL-1的作用，并可能独立于外周活动的IL-1在血流中循环。
In the acute phase of bacterial infection, a variety of cytokines, including interleukin-1 (IL-1), are elicited by bacterial endotoxin in both the periphery and the central nervous system. Bacterial endotoxin has been previously reported to profoundly activate the hypothalamic-pituitary-adrenal axis, resulting in elevated glucocorticoid secretion that may serve an important role as part of the inhibitory feedback mechanisms on the activated immune system. To determine whether IL-1 acts within the brain to mediate endotoxin-induced CRH gene expression in the hypothalamic paraventricular nucleus (PVN), we studied the effect of administering the human IL-1 receptor antagonist (IL-1ra) into the brain, a competitive inhibitor of IL-1, on CRH gene expression in the PVN after systemic lipopolysaccharide (LPS) treatment. Eight hours after the ip administration of LPS, the paraventricular CRH mRNA content was elevated 3-to 4-fold (P 0.05 compared to controls). In contrast, systemic IL-1ra administration did not inhibit endotoxin-induced CRH gene expression in the PVN. These studies demonstrate that LPS stimulates hypothalamic CRH by a mechanism that involves the action of IL-1 within the central nervous system and may proceed independently of peripheral actions of IL-1 circulating in the bloodstream.