Abstract

Introduction The vagus nerve is the main neural substrate of the parasympathetic nervous system and has a role in modulating inflammation through the cholinergic anti-inflammatory pathway, via inhibition of the production of pro-inflammatory cytokines at the level of both the spleen and the intestinal muscularis. Animal studies have demonstrated that in vagotomised mice, electrical vagal nerve stimulation (VNS), applied distal to the severance, ameliorates the pro-inflammatory cytokine response to lipopolysaccharide. The cervical vagus nerve is located directly under the skin, making it a suitable target for transcutaneous non-invasive VNS (n-VNS). In this pilot study, we sought to evaluate the effect of non- n-VNS on pro-inflammatory cytokines and cardiometrically derived autonomic parameters in humans. Methods In healthy volunteers, heart rate, blood pressure and validated sympathetic, (cardiac sympathetic index) and vagal, (cardiac vagal tone (CVT)) indices were measured directly before, and 24 hours after, 2 minutes of n-VNS applied bilaterally. Venous blood was also drawn and assayed for pro-inflammatory cytokines (tumour necrosis factor-alpha (TNF-a) and interferon-gamma (IFN-g)) and the anti-inflammatory cytokine (interleukin-10) directly prior to, and 24 hours after n-VNS. Results 20 healthy volunteers (13 females, median age 34 years, range 23–55) all tolerated the n-VNS. Table 1 details the changes in the recorded parameters. There was a negative correlation between change in CVT and change TNF-a (rs = 0.45, p Conclusion These results, for the first time in humans, provide preliminary evidence for an anti-TNF-a in response to n-VNS, potentially mediated by an increase cardiac vagal tone. These data, warrant further investigation in immune mediated inflammatory disorders such as those with inflammatory bowel disease. Disclosure of Interest None Declared

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