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

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 LXA 4 ) 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.