Vagal afferent activation suppresses systemic inflammation via the splanchnic anti-inflammatory pathway.


Author: Komegae EN1, Stephen Farmer DG2, Brooks VL3, McKinley MJ4, McAllen RM5, Martelli D6

Affiliation: <sup>1</sup>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, 3010, Australia; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

<sup>2</sup>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, 3010, Australia.

<sup>3</sup>Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, USA.

<sup>4</sup>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, 3010, Australia; Department of Physiology, University of Melbourne, Australia.

<sup>5</sup>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, 3010, Australia. Electronic address: rmca@florey.edu.au.

<sup>6</sup>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, 3010, Australia; Department of Biomedical and Neuromotor Science (DIBINEM), University of Bologna, Bologna, Italy. Electronic address: d.martelli@unibo.it.
Conference/Journal: Brain Behav Immun.
Date published: 2018 Jun 5
Other:
  Pages: S0889-1591(18)30221-6   ,  Special Notes: doi: 10.1016/j.bbi.2018.06.005. [Epub ahead of print]   ,  Word Count: 216  
    Electrical stimulation of the vagus nerve (VNS) is a novel strategy used to treat inflammatory conditions. Therapeutic VNS activates both efferent and afferent fibers; however, the effects attributable to vagal afferent stimulation are unclear. Here, we tested if selective activation of afferent fibers in the abdominal vagus suppresses systemic inflammation. In urethane-anesthetized rats challenged with lipopolysaccharide (LPS, 60µg/kg, i.v.), abdominal afferent VNS (2 Hz for 20 mins) reduced plasma tumor necrosis factor alpha (TNF) levels 90 minutes later by 88% compared with unmanipulated animals. Pre-cutting the cervical vagi blocked this anti-inflammatory action. Interestingly, the surgical procedure to expose and prepare the abdominal vagus for afferent stimulation ('vagal manipulation') also had an anti-inflammatory action. Levels of the anti-inflammatory cytokine IL-10 were inversely related to those of TNF. Prior bilateral section of the splanchnic sympathetic nerves reversed the anti-inflammatory actions of afferent VNS and vagal manipulation. Sympathetic efferent activity in the splanchnic nerve was shown to respond reflexly to abdominal vagal afferent stimulation. These data demonstrate that experimentally activating abdominal vagal afferent fibers suppresses systemic inflammation, and that the efferent neural pathway for this action is in the splanchnic sympathetic nerves.



KEYWORDS: Endotoxemia; Greater splanchnic nerve; Inflammation; Interleukin 10 (IL-10); Lipopolysaccharide (LPS); Splanchnic anti-inflammatory pathway; Sympathetic nervous system; Tumor necrosis factor α (TNF); Vagus nerve; Vagus nerve stimulation



PMID: 29883598  DOI: 10.1016/j.bbi.2018.06.005