Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: A randomized controlled study

Abstract

Introduction: Vagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarce. Transvenous VNS (tVNS) is a newly developed and less invasive method to stimulate the vagus nerve. In the present study, we determined whether tVNS is a feasible and safe procedure and investigated its putative anti-inflammatory effects during experimental human endotoxemia. Methods: We performed a randomized double-blind sham-controlled study in healthy male volunteers. A stimulation catheter was inserted in the left internal jugular vein at spinal level C5-C7, adjacent to the vagus nerve. In the tVNS group (n = 10), stimulation was continuously performed for 30 minutes (0-10 V, 1 ms, 20 Hz), starting 10 minutes before intravenous administration of 2 ng kg-1 Escherichia coli lipopolysaccharide (LPS). Sham-instrumented subjects (n = 10) received no electrical stimulation. Results: No serious adverse events occurred throughout the study. In the tVNS group, stimulation of the vagus nerve was achieved as indicated by laryngeal vibration. Endotoxemia resulted in fever, flu-like symptoms, and hemodynamic changes that were unaffected by tVNS. Furthermore, plasma levels of inflammatory cytokines increased sharply during endotoxemia, but responses were similar between groups. Finally, cytokine production by leukocytes stimulated with LPS ex vivo, as well as neutrophil phagocytosis capacity, were not influenced by tVNS. Conclusions: tVNS is feasible and safe, but does not modulate the innate immune response in humans in vivo during experimental human endotoxemia. Trial registration: Clinicaltrials.gov NCT01944228. Registered 12 September 2013.