Short-term transcutaneous non-invasive vagus nerve stimulation may reduce disease activity and pro-inflammatory cytokines in rheumatoid arthritis: results of a pilot study.

Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA. Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS. Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = -0.37, p = 0.03). Overall, n-VNS was well tolerated. Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.

Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha.

The vagus nerve is a central component of cholinergic anti-inflammatory pathways. We sought to evaluate the effect of bilateral transcutaneous cervical vagal nerve stimulation (t-VNS) on validated parameters of autonomic tone and cytokines in 20 healthy subjects. 24 hours after t-VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor-α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t-VNS exerts an autonomic and a subtle antitumor necrosis factor-α effect, which warrants further evaluation in larger controlled studies.

Treatment of rheumatoid arthritis with a peptide diet: a randomized, controlled trial.

Elemental diets provide food in its simplest formulation and have been used in the treatment of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Such a diet is supposed to be less antigenic to the human immune system than normal food. The aim of this study was to evaluate the clinical effect of an artificial peptide diet as a temporary supplement to conventional treatment. Patients with active RA were single-blindly randomized either to a liquid elemental peptide-diet for four weeks or to continuation of the usual food (control group). In the diet group all normal foods were renounced. Thirty patients were included and followed for six months. The outcome measurements were pain intensity, morning stiffness, HAQ-score, number of swollen joints, joint tenderness, erythrocyte sedimentation rate, and patient's global assessment of health. Two of the fifteen patients assigned to the diet dropped out. The diet resulted in a transient but statistically significant improvement in the average level of pain (P = 0.02), in HAQ-score (P=0.03), and a significant reduction in Body Mass Index (P=0.001). Only one patient in the diet group had a clear remission. Side-effects were frequent but compliance good. The study showed that the peptide diet can improve some subjective and objective disease parameters. Due to the low remission ratio the peptide diet is not a treatment of choice in unselected RA-patients. but the peptide diet might be beneficial to a subset of RA-patients, e.g. patients where foods aggravate disease activity.