The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy

Abstract

Biological therapeutics targeting TNF, IL-1, and IL-6 are widely used for treatment of rheumatoid arthritis, inflammatory bowel disease, and a growing list of other syndromes, often with remarkable success. Now advances in neuroscience have collided with this therapeutic approach, perhaps rendering possible the development of nerve stimulators to inhibit cytokines. Action potentials transmitted in the vagus nerve culminate in the release of acetylcholine that blocks cytokine production by cells expressing acetylcholine receptors. The molecular mechanism of this cholinergic antiinflammatory pathway is attributable to signal transduction by the nicotinic alpha 7 acetylcholine receptor subunit, a regulator of the intracellular signals that control cytokine transcription and translation. Favorable preclinical data support the possibility that it may be possible to add nerve stimulators to the future therapeutic armamentarium, possibly replacing some drugs to inhibit cytokines.

The Irritable Bowel Syndrome: How Stress Can Affect the Amygdala Activity and the Brain-Gut Axis

“…In the case of a deficit in PFC activity with a lack of inhibitory regulatory communications with the amygdala, a chronic imbalance of the ANS with an increase sympathetic activity should appear as we have observed in IBS patients exhibiting a low heart rate variability and a high score of anxiety (Pellissier, et al 2010a). Moreover, there is a strong relation between the activity of the ANS and the immune system as recently shown by the cholinergic anti-inflammatory pathway (Huston and Tracey 2011). Hence, when the parasympathetic system is hypoactive as a consequence of anxiety for instance, it could facilitate inflammation which could be deleterious for health and well-being (Bonaz 2003).…”

Meditation: Should a cardiologist care?

“…Efferent vagal activity is then enhanced and information relayed to the spleen and other organs where proinflammatory cytokines are inhibited and inflammation is limited. [31][32][33] (Figure 2)…”

The Role of Fish Oil Feeding Rich in ω‐3 Polyunsaturated Fatty Acids in Patients with Sepsis and Septic Shock

“…In the case that HRV metrics predict outcomes of interest, such as lower infection rate and/or attenuated organ dysfunction, such a study might identify a unique value of HRV analysis as a monitoring tool of inflammatory modulation by fish oil feeding, in septic patients. Another potential use of HRV in artificial nutrition of septic patients as has been suggested by Tracey [62] could be its adoption as a physiomarker to early identify patients with reduced vagal tone. In this case, a susceptibility to increased inflammation can be assumed, whereas HRV metrics might serve as an early alarm to identify patients who might benefit from pharmacological stimulation of the cholinergic anti-inflammatory pathway, such as ω-3 PUFAs [62].…”