Miksa Michael, Wu Rongqian, Zhou Mian, Wang Ping
Division of Surgical Research, North Shore Hospital and Long Island Jewish Medical Center, Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
Front Biosci. 2005 Sep 1;10:2217-29. doi: 10.2741/1691.
In the history of medicine, the interaction between mind and body has been repeatedly proposed. However, the influence of the nervous system on the immune regulation has, until now, drawn little attention. In this regard, the adrenergic system has been explored, and mainly catecholamine-mediated anti-inflammatory effects have been described. These inhibitory effects of epinephrine and norepinephrine were found to be mediated by beta2-adrenoceptors expressed on mononuclear cells. Recently, the role of the parasympathetic nervous system in the local anti-inflammatory reflex has been investigated. Stimulation of the vagus nerve decreases the pro-inflammatory response of macrophages via alpha7-cholinergic receptors. Thus, both the sympathetic and parasympathetic nervous systems are thought to work hand in hand in their anti-inflammatory responses. Here we discuss the deteriorating effects of the release of norepinephrine in sepsis. We have discovered that organ dysfunction in severe sepsis is mediated at least in part by an increase in pro-inflammatory cytokine release from Kupffer cells, which is caused by a priming via gut-derived norepinephrine. The sympathetic nervous system and gut-derived norepinephrine mediate the pro-inflammatory effects by activating alpha2A-adrenoceptor on Kupffer cells. In this review, we will focus on the differential function of the noradrenergic system on local and systemic inflammatory responses and the possibilities of the modulation of sympathetic outflow by centrally active inhibitors such as the novel peptide ghrelin or NMDA-receptor blockers. Furthermore, we will introduce the new concept of "sympathetic excitotoxicity in sepsis" characterized by the neurogenic priming of the systemic pro-inflammatory response.
在医学史上，身心之间的相互作用已被反复提出。然而，迄今为止，神经系统对免疫调节的影响几乎未受到关注。在这方面，人们已经对肾上腺素能系统进行了探索，并且主要描述了儿茶酚胺介导的抗炎作用。发现肾上腺素和去甲肾上腺素的这些抑制作用是由单核细胞上表达的β2-肾上腺素能受体介导的。最近，副交感神经系统在局部抗炎反射中的作用也得到了研究。刺激迷走神经可通过α7-胆碱能受体降低巨噬细胞的促炎反应。因此，交感神经系统和副交感神经系统被认为在抗炎反应中携手合作。在此，我们讨论脓毒症中去甲肾上腺素释放的恶化作用。我们发现，严重脓毒症中的器官功能障碍至少部分是由库普弗细胞促炎细胞因子释放增加介导的，而这是由肠道来源的去甲肾上腺素引发的。交感神经系统和肠道来源的去甲肾上腺素通过激活库普弗细胞上的α2A-肾上腺素能受体介导促炎作用。在这篇综述中，我们将重点关注去甲肾上腺素能系统在局部和全身炎症反应中的不同功能，以及通过新型肽胃饥饿素或NMDA受体阻滞剂等中枢活性抑制剂调节交感神经输出的可能性。此外，我们将介绍“脓毒症中的交感兴奋毒性”这一新概念，其特征是全身促炎反应的神经源性引发。
