A central mechanism is involved in the secretion of ACTH in response to IL-6 in rats: comparison to and interaction with IL-1 beta.
A central mechanism is involved in the secretion of ACTH in response to IL-6 in rats: comparison to and interaction with IL-1 beta.
复制标题
大鼠中响应 IL-6 分泌 ACTH 的核心机制涉及：与 IL-1 β 的比较和相互作用。
DOI：
10.1159/000126269
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发表时间：
1992
影响因子：
4.1
通讯作者：
Sharp,BM
中科院分区：
文献类型：
--
作者：
Matta,SG;Weatherbee,J;Sharp,BM
已知细胞因子白介素-1β (IL-1β)、白介素-6 （IL-6）和肿瘤坏死因子-α是促肾上腺皮质激素分泌的有效影响因子。IL-1β的一些外周作用似乎与IL-1β诱导的IL-6分泌有关。因此，我们评估了IL-6对ACTH分泌的影响及其与IL-1β的相互作用。大鼠颈静脉留置重组人（ril -6）或鼠（ril -6） IL-6。rhIL-6 （200 ng或2µg/大鼠）产生的峰值血浆ACTH水平比基础水平高3- 4倍。rmIL-6产生了类似的反应。两种IL-6均不影响血浆催乳素水平。ril -1β (200 ng)与ril -6（200、100和50 ng）的比较表明，IL-6以剂量依赖性的方式升高ACTH， IL-1β明显更有效。IL-1β与IL-6同时或在IL-6后10分钟给予。IL-1lβ（100,30或10 ng）和IL-6 （100 ng）一起给药时产生的ACTH水平明显高于单独给药时。当IL-6比IL-1β早给药10分钟时，这种可加性也很明显。IL-6（2µg）与促肾上腺皮质激素释放因子（CRF, 1µg/kg, b.w）共同给药对促肾上腺皮质激素分泌也有累加效应（在20分钟：CRF为300±40 pg/ml， IL-6为320±83 pg/ml， CRF+ IL-6为540±44 pg/ml），而更高剂量的CRF（10µg/kg b.w）在20分钟产生的ACTH水平为1000±107 pg/ml， IL-6没有进一步增强。单独IL-6（0.1、1.0或3.0 nM）孵育垂体细胞时，高剂量IL-6在2 h内对ACTH分泌产生轻微但显著的刺激（p < 0.05），但未改变体外CRF的作用。为了确定IL-6的作用是否在脑内的某个部位，将IL-6（30或100 ng/0.5µl）注射到警觉大鼠的第三脑室。100ng IL-6在30min内引起血浆ACTH峰值（300±65 pg/ml）；这些反应显著高于缓冲反应（90±25 pg/ml, p < 0.01），低于30 ng IL-1β的反应（530±50 pg/ml, p < 0.001）。30 ng IL-6无效。直接靠近中位隆起的肺实质内注射IL-6（25或125 ng/0.4µl）或IL-1β(5或25 ng/0.4µl)，在30分钟时，两者的高剂量均显著升高ACTH反应：IL-1β后229±27 pg/ml， IL-6后157±17 pg/ml，缓冲后64±12 pg/ml （p < 0.05）。相比之下，在靠近室旁核给药后，血浆ACTH水平仅在高剂量IL-1β的作用下升高：在30分钟时，与缓冲剂117±17 pg/ml相比，血浆ACTH水平为206±31 pg/ml （p < 0.05）。因此，IL-6是一种促ACTH分泌剂，可能在脑内起作用，仅部分作用于正中隆起水平。由于IL-6的作用与CRF是叠加的，IL-6似乎诱导CRF的分泌，从而诱导ACTH。IL-6的效果远不如IL-1β，但它也可以与后者一起添加，后者是一种已知的CRF分泌剂。
The cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α are known to be potent effectors of ACTH secretion. Some of the peripheral effects of IL-1β appear to be related to the secretion of IL-6 induced by IL-1β. Thus, we evaluated the effect of IL-6 on ACTH secretion and its interaction with IL-1β. Rats received recombinant human (rhIL-6) or murine (rmIL-6) IL-6 through indwelling jugular cannulae. rhIL-6 (200 ng or 2 µg/rat) produced peak plasma ACTH levels which were 3- to 4-fold greater than basal levels. rmIL-6 produced similar responses. Neither species of IL-6 affected plasma prolactin levels. Comparison of rhIL-1β (200 ng) to rhIL-6 (200, 100 or 50 ng) showed that IL-6 elevated ACTH in a dose-dependent manner and that IL-1β was significantly more effective. IL-1β was also administered concomitantly with or 10 min after IL-6. Delivered together, IL-1lβ (100, 30 or 10 ng) and IL-6 (100 ng) produced significantly higher ACTH levels than when given alone. This additivity was also evident when IL-6 was given 10 min prior to IL-1β. The coadministration of IL-6 (2 µg) with corticotropin-releasing factor (CRF, 1 µg/kg, b.w.) also had an additive effect on ACTH secretion (at 20 min: 300 ± 40 pg/ml for CRF; 320 ± 83 pg/ml for IL-6; and 540 ± 44 pg/ml for CRF+ IL-6), whereas a higher dose of CRF (10 µg/kg b.w.) yielded ACTH levels of 1,000 ± 107 pg/ml at 20 min, with no further enhancement by IL-6. Incubation of pituitary cells with IL-6 alone (0.1, 1.0 or 3.0 nM) produced a slight but significant stimulation of ACTH secretion within 2 h in response to the higher doses of IL-6 only (p < 0.05), but did not modify the effect of CRF in vitro. To determine if the action of IL-6 was at a site(s) within the brain, IL-6 (30 or 100 ng/0.5 µl) was injected into the third cerebroventricle of alert rats. 100 ng IL-6 elicited peak plasma ACTH levels (300 ± 65 pg/ml) within 30 min; these were significantly higher than the buffer responses (90 ± 25 pg/ml, p < 0.01), and lower than the responses to 30 ng IL-1β (530 ± 50 pg/ml, p < 0.001). 30 ng IL-6 was ineffective. Intraparenchymal injection of IL-6 (25 or 125 ng/0.4 µl) or IL-1β (5 or 25 ng/0.4 µl) directly adjacent to the median eminence produced a significant elevation in the ACTH response to the higher dose of each at 30 min: 229 ± 27 pg/ml after IL-1β or 157 ± 17 pg/ml after IL-6 compared to 64 ± 12 pg/ml after buffer (p < 0.05). In contrast, after administration adjacent to the paraventricular nucleus, plasma ACTH levels were elevated only in response to the higher dose of IL-1β: at 30 min, 206 ± 31 pg/ml compared to buffer 117 ± 17 pg/ml (p < 0.05). Thus, IL-6 is an ACTH secretagogue which may act within the brain, only in part at the level of the median eminence. Since the effect of IL-6 was additive with CRF, IL-6 appears to induce the secretion of CRF and, thereby, ACTH. IL-6, which was much less effective than IL-1β was also additive with the latter which is known to be a CRF secretagogue.