The purpose of this study is to assess the effect of transvenous vagus nerve stimulation (tVNS) on the immune response.

In the human endotoxemia model, intravenously administered endotoxin (lipopolysaccharide [LPS]) elicits a systemic immune response with release of pro-inflammatory cytokines, such as TNF α. This trial will determine if an anti-inflammatory effect can be produced by acute VNS using a minimally invasive delivery method.

Inclusion Criteria:

1. Written informed consent to participate in this trial
2. Male subjects aged 18 to 35 years inclusive
3. Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters

Exclusion Criteria:

• Use of any medication(including herbal remedies and vitamin/mineral supplements) or recreational drugs within 7 days prior to profiling day
• Smoking
• Use of caffeine, or alcohol or within 1 day prior to profiling day
• Previous participation in a trial where LPS was administered
• Surgery or trauma with significant blood loss or blood donation within 3 months prior to profiling day
• Participation in another clinical trial within 3 months prior to profiling day.
• History, signs or symptoms of cardiovascular disease
• An implant that in the opinion of the investigator may make invasive procedures risky for the subject due to the increased risks associated with a possible infection.
• Subject has an implanted active cardiac device (ICD, IPG and/or CRT)
• Implanted active neurostimulation device
• Subject has internal jugular vein that cannot be accessed
• History of vaso-vagal collapse or of orthostatic hypotension
• History of atrial or ventricular arrhythmia
• Resting pulse rate ≤45 or ≥100 beats / min
• Hypertension (RR systolic >160 or RR diastolic >90)
• Hypotension (RR systolic <100 or RR diastolic <50)
• Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
• Subject is diagnosed with epilepsy or history of seizures
• Renal impairment: plasma creatinine >120 µmol/L
• Liver function abnormality: alkaline phosphatase>230 U/L and/or ALT>90 U/L
• Coagulation abnormalities: APTT or PT > 1.5 times the reference range
• History of asthma
• Immuno-deficiency
• CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 2 weeks before profiling day
• Known or suspected of not being able to comply with the trial protocol
• Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.