Päth G, Bornstein S R, Ehrhart-Bornstein M, Scherbaum W A
Department of Internal Medicine III, University of Leipzig, Germany.
J Clin Endocrinol Metab. 1997 Jul;82(7):2343-9. doi: 10.1210/jcem.82.7.4072.
Interleukin (IL)-6 is a potent activator of the human hypothalamicpituitary-adrenal axis. After chronic administration of IL-6 in humans, there is a substantial elevation of cortisol, whereas ACTH levels are blunted. Thus, we investigated whether IL-6 and/or the IL-6 receptor (IL-6R) are expressed in the human adrenal gland and whether IL-6 could cause the release of steroid hormones by a direct action on adrenal cells in primary culture. The expression of IL-6 and IL-6R was investigated with RT-PCR and immunohistochemistry, and the effects on human adrenal steroidogenesis were tested with IL-6 in vitro. To avoid effects mediated by macrophages, we depleted adrenal primary cultures from macrophages using specific mouse antihuman CD68 and sheep antimouse IgG conjugated magnetic beads. The results showed that 1): IL-6 and IL-6R are expressed in adrenal cell cultures, including all cell types and those depleted of macrophages; 2) IL-6R is mainly expressed in the zona reticularis and the inner zona fasciculata; positive signals from the zona glomerulosa and the medulla occurred in single cells; and 3) IL-6 regulates adrenal synthesis of mineralocorticoids, glucocorticoids, and androgens in vitro, dependent on time and dose, in the absence of macrophages. After 24 h, aldosterone secretion increased to 172 +/- 28% SEM, cortisol to 177 +/- 27% SEM, and dehydroepiandrosterone to 153 +/- 20% SEM of basal secretion. These findings, in combination with previous investigations, suggest that IL-6 exerts its acute action via the hypothalamus and the pituitary. In the adrenal gland, however, IL-6 seems to be a long-term regulator of stress response, integrating the responses of all cortical zones to stimuli from the immune and endocrine system.
白细胞介素（IL）-6是人类下丘脑-垂体-肾上腺轴的强效激活剂。在人类长期给予IL-6后，皮质醇水平显著升高，而促肾上腺皮质激素（ACTH）水平则降低。因此，我们研究了IL-6和/或IL-6受体（IL-6R）是否在人类肾上腺中表达，以及IL-6是否能通过直接作用于原代培养的肾上腺细胞来导致类固醇激素的释放。采用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学方法研究了IL-6和IL-6R的表达，并在体外使用IL-6测试其对人类肾上腺类固醇生成的影响。为避免巨噬细胞介导的效应，我们使用特异性小鼠抗人CD68和羊抗小鼠IgG偶联磁珠从肾上腺原代培养物中去除巨噬细胞。结果显示：1）IL-6和IL-6R在肾上腺细胞培养物中表达，包括所有细胞类型以及去除巨噬细胞的细胞培养物；2）IL-6R主要表达于网状带和束状带内层；球状带和髓质的单个细胞出现阳性信号；3）在没有巨噬细胞的情况下，IL-6在体外调节盐皮质激素、糖皮质激素和雄激素的肾上腺合成，其作用依赖于时间和剂量。24小时后，醛固酮分泌增加至基础分泌的172±28%（标准误），皮质醇增加至177±27%（标准误），脱氢表雄酮增加至153±20%（标准误）。这些发现与先前的研究相结合，表明IL-6通过下丘脑和垂体发挥其急性作用。然而，在肾上腺中，IL-6似乎是应激反应的长期调节因子，整合了所有皮质区对来自免疫和内分泌系统刺激的反应。
