Continuous vs. intermittent chronic vagus nerve stimulation: effects on T-cell dependent antibody response, heart...

Vagal-immune interactions are increasingly recognized to play a role in the pathogenesis of diseases associated with immune dysfunction. To study the direct effects of altered vagal activity on adaptive immune function and antibody production, we modeled a state of elevated vagal activation by delivering chronic vagus nerve stimulation (VNS) in immunized mice. We delivered VNS for 14 days before and 14 days after immunization with an antigen, using 2 schedules: Twice Daily VNS, to model intermittently elevated vagal activity, and Continuous Burst VNS, to model chronically elevated vagal activity. We found that Continuous Burst VNS is associated with increased heart rate variability (HRV) on the first week of treatment, remodeling of cellular splenic compartments, as well as weight loss. Such changes are not seen with Twice Daily VNS. High-affinity antibody production is reduced with both Continuous Burst and Twice Daily VNS, compared to no VNS. Total IgG antibody titers are reduced in Continuous Burst VNS, even prior to immunization, likely an effect of weight loss. In conclusion, both continuously and intermittently elevated vagal tone limits the antibody response. Nonselective, whole nerve VNS produces multiple effects that may confound interpretation of specific immune effects at higher stimulation doses.