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昼夜节律依赖性肝脊髓轴门控在大鼠中引发抗炎反射。

Time-of-Day-Dependent Gating of the Liver-Spinal Axis Initiates an Anti-Inflammatory Reflex in the Rat.

机构信息

Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México 04510, México.

Departamento de Anatomía, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, México.

出版信息

eNeuro. 2020 Dec 10;7(6). doi: 10.1523/ENEURO.0463-20.2020. Print 2020 Nov/Dec.

DOI:10.1523/ENEURO.0463-20.2020
PMID:33203733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7729296/
Abstract

The autonomic nervous system (ANS) modulates the immune response through the engagement of an anti-inflammatory reflex. There is controversy regarding which efferent branch of the ANS, sympathetic or parasympathetic, downregulates the intensity of the inflammatory response. Furthermore, how information about the immune status of the body reaches the CNS to engage this reflex remains unclear. The present study demonstrates the existence of a liver-spinal axis that conveys early circulating inflammatory information to the CNS in response to lipopolysaccharide (LPS) and serves as the afferent arm of a sympathetic anti-inflammatory reflex. Furthermore, brainstem and spinal cord visceral sensory neurons show a time-of-day-dependent sensitivity to the incoming inflammatory information, in particular, prostaglandins (PG). Consequentially, the liver-spinal axis promotes the retention of tumor necrosis factor α (TNFα) in the liver and spleen during the resting period, resulting in low plasmatic TNFα levels. Consistently, low sensitivity for LPS during the active period promotes the release of TNFα from the organs into the circulation, resulting in high plasmatic TNFα levels. The present novel findings illustrate how the time-of-day-dependent activation of the liver-spinal axis contributes to the daily fluctuations of the inflammatory response.

摘要

自主神经系统 (ANS) 通过抗炎反射来调节免疫反应。关于哪条 ANS 传出分支（交感神经或副交感神经）下调炎症反应的强度存在争议。此外，关于身体免疫状态的信息如何到达中枢神经系统以启动这种反射仍然不清楚。本研究证明了存在一个肝脊髓轴，它可以将早期循环炎症信息传递到中枢神经系统，以响应脂多糖 (LPS)，并作为交感抗炎反射的传入臂。此外，脑干和脊髓内脏感觉神经元对传入的炎症信息，特别是前列腺素 (PG)，表现出时间依赖性敏感性。因此，肝脊髓轴在休息期间将肿瘤坏死因子 α (TNFα) 保留在肝脏和脾脏中，导致血浆 TNFα 水平较低。一致地，在活动期对 LPS 的低敏感性促进了 TNFα 从器官释放到循环中，导致血浆 TNFα 水平升高。本新发现说明了肝脊髓轴的时间依赖性激活如何导致炎症反应的日常波动。

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