Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45237-1625, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Jul;299(1):R343-51. doi: 10.1152/ajpregu.00131.2010. Epub 2010 Apr 28.
An emerging literature attests to the ability of psychological stress to alter the inflammatory cytokine environment of the body. While the ability of stress to cause cytokine release is well established, the neural pathways involved in this control have yet to be identified. This study tests the hypothesis that IL-6 neurons of the hypothalamo-neurohypophyseal system (HNS), a neural pathway proposed to secrete IL-6 into the circulation, are activated in response to psychological stress. Colocalization studies confirm robust expression of IL-6 in cell bodies and fibers of vasopressin (but not oxytocin) neurons of the paraventricular (PVN) and supraoptic nucleus (SON) of the rat hypothalamus. In response to restraint, there was a greater increase in c-Fos expression in SON IL-6-positive (IL-6+) neurons. In addition, both psychogenic (restraint) or systemic stress (hypoxia) lead to phosphorylated ERK induction only in IL-6+ magnocellular neurons, indicating selective activation of the MAPK signaling pathway in the IL-6 subset of magnocellular neurons. Finally, restraint upregulated IL-6 mRNA expression in both the PVN and SON, which was accompanied by a four-fold increase in circulating IL-6. The data indicate that noninflammatory stressors selectively activate IL-6 magnocellular neurons, upregulate IL-6 gene expression in the PVN and SON, and increase plasma IL-6. In summary, results show that IL-6 neurons of the HNS are a recruited component of the response to psychological stress.
新兴文献证明，心理压力能够改变身体的炎症细胞因子环境。虽然压力导致细胞因子释放的能力已经得到证实，但涉及这种控制的神经途径尚未确定。本研究检验了这样一个假设，即下丘脑神经垂体系统（HNS）的 IL-6 神经元——一种被提议将 IL-6 分泌到循环中的神经途径——会在心理压力下被激活。共定位研究证实，大鼠下丘脑室旁核（PVN）和视上核（SON）的加压素（但不是催产素）神经元的细胞体和纤维中，IL-6 表达丰富。在受到束缚时，SON 中 IL-6 阳性（IL-6+）神经元的 c-Fos 表达增加更为显著。此外，无论是心理性（束缚）还是全身性应激（缺氧），都只会诱导 IL-6+大细胞神经元中磷酸化 ERK 的诱导，表明 MAPK 信号通路在 IL-6 大细胞神经元亚群中被选择性激活。最后，束缚会增加 PVN 和 SON 中 IL-6 的 mRNA 表达，同时循环中的 IL-6 增加了四倍。数据表明，非炎症性应激源选择性地激活了 IL-6 大细胞神经元，上调了 PVN 和 SON 中 IL-6 的基因表达，并增加了血浆中的 IL-6。总之，结果表明 HNS 的 IL-6 神经元是对心理应激反应的一个被募集的组成部分。
