Cutting Edge: Human Vagus Produces Specialized Proresolving Mediators of Inflammation with Electrical Stimulation Reducing Proinflammatory Eicosanoids.

Author: Serhan CN1, de la Rosa X2, Jouvene CC2
Author Information:
1Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 cserhan@bwh.harvard.edu.
2Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
Conference/Journal: J Immunol.
Date published: 2018 Oct 24
Other: Pages: ji1800806 , Special Notes: doi: 10.4049/jimmunol.1800806. [Epub ahead of print] , Word Count: 160


Inflammatory resolution is a process that, when uncontrolled, impacts many organs and diseases. As an active, self-limited inflammatory process, resolution involves biosynthesis of specialized proresolving mediators (SPM) (e.g., lipoxins, resolvins [Rv], protectins, and maresins). Because vagal stimulation impacts inflammation, we examined human and mouse vagus ex vivo to determine if they produce lipid mediators. Using targeted lipid mediator metabololipidomics, we identified lipoxins, Rv, and protectins produced by both human and mouse vagus as well as PGs and leukotrienes. Human vagus produced SPM (e.g., RvE1, NPD1/PD1, MaR1, RvD5, and LXA4) on stimulation that differed from mouse (RvD3, RvD6, and RvE3), demonstrating species-selective SPM. Electrical vagus stimulation increased SPM in both human and mouse vagus as did incubations with Escherichia coli. Electrical vagus stimulation increased SPM and decreased PGs and leukotrienes. These results provide direct evidence for vagus SPM and eicosanoids. Moreover, they suggest that this vagus SPM circuit contributes to a new proresolving vagal reflex.

PMID: 30355784 DOI: 10.4049/jimmunol.1800806