The role of interleukin-6 in the activation of the hypothalamo-pituitary-adrenocortical axis and brain indoleamines by endotoxin and interleukin-1β
The role of interleukin-6 in the activation of the hypothalamo-pituitary-adrenocortical axis and brain indoleamines by endotoxin and interleukin-1β
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DOI：
10.1016/s0006-8993(98)01091-9
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发表时间：
1999-01
期刊：
影响因子：
2.9
通讯作者：
Jianping Wang;A. Dunn
中科院分区：
文献类型：
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作者：
Jianping Wang;A. Dunn
白介素6(IL-6)是刺激下丘脑-垂体-肾上腺皮质(HPA)轴的几种细胞因子之一。由于IL-6是内毒素(LPS)和白介素1(IL-1)作用下的产物，因此IL-6可能参与了内毒素和白介素1引起的神经内分泌和神经化学变化。在本研究中，腹腔注射(i.p.)注射脂多糖可升高血浆IL-6浓度，同时激活HPA轴，并呈剂量依赖关系。给小鼠IL-1β(100ng.ip)后2-3h左右，两种反应均达到高峰。小鼠腹腔注射抗IL-6单抗后，血浆ACTH和皮质酮水平在3h显著降低，但1h无明显变化，抗IL-6治疗也可抑制内毒素引起的色氨酸和5-羟色胺分解代谢产物5-羟吲哚乙酸(5-HIAA)的升高，但对去甲肾上腺素分解代谢产物3-甲氧基-4-羟基苯乙二醇(MHPG)无明显影响。IL-6抗体可显著抑制IL-1诱导的小鼠血浆ACTH和皮质酮的升高，但在4h时无明显变化，但对IL-1诱导的下丘脑和脑干组织中MHPG、色氨酸和5-HIAA的升高无明显影响。这些结果表明，IL-6参与了内毒素和IL-1刺激HPA轴的后期阶段，并参与了对内毒素的吲哚胺能反应，但对IL-1没有作用。
Interleukin-6 (IL-6) is one of several cytokines that can stimulate the hypothalamo-pituitary-adrenocortical (HPA) axis. Because IL-6 is produced in response to the administration of endotoxin (LPS) and interleukin-1 (IL-1), it is possible that IL-6 contributes to the neuroendocrine and neurochemical changes induced by them. In this study, intraperitoneal (i.p.) injection of LPS elevated plasma concentrations of IL-6 while activating the HPA axis in a dose-dependent manner. Both responses reached a peak at around 2–3 h. Mouse IL-1β administration (100 ng, i.p.) induced large increases in plasma corticosterone and a substantial, but short-lived increase in plasma IL-6 with a peak at 2 h. Pretreatment of mice intraperitoneally with a monoclonal antibody to mouse IL-6 significantly attenuated the plasma ACTH and corticosterone responses to LPS at 3 h, but not at 1 h. Anti-IL-6 treatment also attenuated the LPS-induced increases of tryptophan and the serotonin catabolite, 5-hydroxyindoleacetic acid (5-HIAA), but not that of the norepinephrine catabolite, 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG). Pretreatment of mice with anti-IL-6 significantly attenuated the IL-1-induced increases of plasma ACTH and corticosterone at 2 h, but not at 4 h. The IL-1-induced increases of MHPG, tryptophan and 5-HIAA in hypothalamus and brain stem were not significantly altered. These results suggest that IL-6 contributes to the later phases of the LPS- and IL-1-induced stimulations of the HPA axis and to the indoleaminergic responses to LPS, but not to IL-1.