Central nervous system administration of interleukin-6 produces splenic sympathoexcitation
Central nervous system administration of interleukin-6 produces splenic sympathoexcitation
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DOI：
10.1016/j.autneu.2008.04.008
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发表时间：
2008-08-18
影响因子：
2.7
通讯作者：
Kenney, Michael J.
中科院分区：
文献类型：
--
作者：
Helwig, Bryan G.;Craig, Robin A.;Kenney, Michael J.
白细胞介素-6（IL-6）是一种多功能细胞因子，已被证明在中枢介导的生理反应中起关键作用，包括激活下丘脑-垂体-肾上腺轴。脑脊髓液（CSF）中IL-6的浓度在多种病理生理条件下升高，包括阿尔茨海默病、自身免疫性疾病和脑膜炎。尽管如此，IL-6对交感神经放电（SND）的中枢调节的作用仍然未知，这限制了对健康和疾病中交感神经-免疫相互作用的理解。在本研究中，我们测定了侧脑室（icv，侧脑室）注射IL-6对氯醛糖麻醉大鼠脾脏SND的影响。第二个目标是确定icv注射的IL-6是否进入脑实质并作为体积传输信号进入参与交感神经流出调节的脑区域。在去压力感受器神经支配的Sprague-Dawley大鼠中，Icv施用IL-6（10 ng、100 ng和400 ng）显著地和进行性地从对照水平增加脾SND。与10 ng剂量相比，100 ng和400 ng IL-6的给药导致显著更高的SND应答。icv给药后60分钟，荧光标记的IL-6没有分布在整个脑实质中，而是定位于脑室系统的脑室周围区域。脑切片对IL-6受体（IL-6 R）进行复染，结果显示IL-6和IL-6 R共定位于毗邻第三脑室的脑室周围区域。这些结果表明icv IL-6给药增加了脾SND，这是一种可能通过起源于室周细胞的信号传导机制实现的效果。(c)2008 Elsevier B.V保留所有权利。
Interleukin-6 (IL-6) is a multifunctional cytokine that has been shown to play a pivotal role in centrally-mediated physiological responses including activation of the hypothalamic-pituitary-adrenal axis. Cerebral spinal fluid (CSF) concentrations of IL-6 are elevated in multiple pathophysiological conditions including Alzheimer's disease, autoimmune disease, and meningitis. Despite this, the effect of IL-6 on central regulation of sympathetic nerve discharge (SND) remains unknown which limits understanding of sympathetic-immune interactions in health and disease. In the present study we determined the effect of intracerebroventricular (icv, lateral ventricle) administration of IL-6 on splenic SND in urethane-chloralose-anesthetized rats. A second goal was to determine if icv injected IL-6 enters the brain parenchyma and acts as a volume transmission signal to access areas of the brain involved in regulation of sympathetic nerve outflow. Icv administration of IL-6 (10 ng, 100 rig, and 400 ng) significantly and progressively increased splenic SND from control levels in baroreceptor-denervated Sprague-Dawley rats. Administration of 100-ng and 400-ng IL-6 resulted in significantly higher SND responses when compared to those elicited with a 10-ng dose. Sixty minutes following icv administration, fluorescently labeled IL-6 was not distributed throughout the parenchyma of the brain but was localized to the periventricular areas of the ventricular system. Brain sections counter-stained for the IL-6 receptor (IL-6R) revealed that IL-6 and the IL-6R were co-localized in periventricular areas adjoining the third ventricle. These results demonstrate that icv IL-6 administration increases splenic SND, an effect likely achieved via signaling mechanisms originating in the periventricular cells. (c) 2008 Elsevier B.V All rights reserved.