Parameters matter: modulating cytokines using nerve stimulation

Abstract

The vagus nerve-based inflammatory reflex regulates inflammation and cytokine release. Recent successful clinical trials using implantable bioelectronic devices to modulate the inflammatory reflex in patients with rheumatoid arthritis and inflammatory bowel disease have demonstrated the efficacy of targeting neural circuits as an efficient alternative to drug treatments. However, the optimal vagus nerve stimulation parameters to achieve efficacious symptomatic relief for inflammation are still unknown. In this issue of Bioelectronic Medicine, Tsaava et al. tested whether altering these electrical stimulation parameters would change circulating cytokine levels in healthy mice. They found that specific combinations of parameters produced significant increases in serum TNF while other parameters selectively lowered serum TNF levels, as compared to sham stimulated mice. These results have considerable implications for determining the optimal stimulation parameters to better treat common conditions and diseases that involve immune regulation.

Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases

“…The optimal parameters of VNS to achieve efficacious inflammation-related symptomatic relief by recruiting the appropriate fibers within the VN are still unknown. Specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the proinflammatory cytokine TNF, while other parameters selectively lowered serum TNF levels, as compared to sham-stimulated mice (Bonaz, 2020;Tsaava et al, 2020). VN morphology influences fiber responses to electrical stimulation.…”

The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia

“…Concerning the effect of VNS on systemic cytokine responses, a critical note is that these responses depend on the stimulation parameters such as frequency, amplitude, and pulse width as was demonstrated by Tsaava et al, and recently reviewed (Tsaava et al 2020 ; Bonaz 2020 ). Although low frequency stimulation (as was used in our studies) was not examined, stimulation with high amplitudes resulted in an increase in IL-6 and decrease in IL-5 and TNF-α.…”

Targeting the anti-inflammatory properties of the vagus nerve through vagus nerve stimulation: Therapeutic implications for inflammatory bowel diseases and other inflammatory conditions

“…It could be an alternative non-drug therapy to conventional treatment or could be combined with such treatments, but further investigation in large longitudinal cohorts of patients is required. Finally, the optimal neurostimulation parameters to better treat common conditions and diseases that involve immune regulation to achieve significant cytokine changes need to be determined (Bonaz 2020).…”

“…Interoception, the sense of the body's internal physiological state, is regarded as the basis for motivational and emotional feelings and to the core neurobiological representation of self. Interoceptive mechanisms appear central to somatic disorders of brain-body interactions, including functional digestive disorders, such as irritable bowel syndrome (IBS), but also IBD (Bonaz et al 2020;Fournier et al 2020).…”