Summary: Electrical stimulation of the vagus nerve promotes healing in people with acute inflammation by altering the balance between inflammatory and anti-inflammatory molecules.
Source: Karolinska Institute
The nervous system is known to communicate with the immune system and regulate inflammation in the body. Researchers from Karolinska Institutet in Sweden are now showing how electrical activation of a specific nerve can promote healing from acute inflammation.
The discovery, published in the journal PNASopens up new avenues to accelerate the resolution of inflammation.
How the body regulates inflammation is only partially understood. Previous research by Peder Olofsson’s group at Karolinska Institutet and other research groups has shown that electrical stimulation of the vagus nerve can reduce inflammation.
Such nerve stimulation has been used with encouraging results in clinical studies on patients with inflammatory bowel disease and rheumatoid arthritis. However, how nerve signals regulate the active resolution of inflammation was unclear.
“We have now studied the effects of signals between nerves and immune cells at the molecular level,” says April S. Caravaca, a researcher in Peder Olofsson’s group at the Solna Department of Medicine, Karolinska Institutet and the Stockholm Center for Bioelectronic Medicine. from MedTechLabs. .
“A better understanding of these mechanisms will enable more precise applications that harness the nervous system to regulate inflammation.”
Researchers have shown that electrical stimulation of the vagus nerve in inflammation alters the balance between specialized inflammatory and anti-inflammatory molecules, which promotes healing.
“Inflammation and its resolution play a key role in a wide range of common diseases, including autoimmune diseases and cardiovascular disease,” explains Peder Olofsson.
“Our findings provide insight into how the nervous system can accelerate the resolution of inflammation by activating defined signaling pathways.”
Researchers will continue to study in more detail how nerves regulate the healing of inflammation.
“The vagus nerve is just one of many nerves that regulate the immune system. We will continue to map the nerve networks that regulate inflammation at the molecular level and investigate how these signals are involved in disease development,” says Dr. Olofsson.
“We hope this research will lead to a better understanding of how pathological inflammation can resolve itself and contribute to more effective treatments for many inflammatory diseases, such as atherosclerosis and rheumatism.”
Funding: The study was supported by grants from the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Heart-Lung Foundation, MedTechLabs and Novo Nordisk. Peder Olofsson owns shares in Emune AB. Co-author Jesmond Dalli is the Founder and Director of Research at Resolomys Ltd.
About this brain stimulation and inflammation research news
Author: Press office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
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Original research: Access closed.
“Vagus nerve stimulation promotes resolution of inflammation through a mechanism that involves Alox15 and requires the α7nAChR subunit” by April S. Caravaca et al. PNAS
Vagus nerve stimulation promotes resolution of inflammation through a mechanism that involves Alox15 and requires the α7nAChR subunit
Non-resolving inflammation underlies a range of chronic inflammatory diseases, and therapeutic acceleration of inflammation resolution may improve outcomes.
Neural reflexes regulate the intensity of inflammation (eg, by signals in the vagus nerve), but it is unknown whether vagus nerve activation promotes resolution of inflammation in vivo.
To study this, mice were subjected to electrical vagus nerve stimulation (VNS) or sham surgery at the cervical level, followed by zymosan-induced peritonitis.
The duration of inflammation resolution was significantly reduced and efferocytosis was significantly increased in mice treated with VNS compared to sham. Lipid mediator (LM) metabololipidomics revealed that mice treated with VNS had higher levels of specialized pro-resolving mediators (SPM), specifically the omega-3 metabolomes docosahexaenoic (DHA) and docosapentaenoic (n-3 DPA), in peritoneal exudates.
VNS also shifted the ratio of pro-inflammatory and pro-resolving LMs to a pro-resolving profile, but this effect by VNS was reversed in mice deficient in 12/15-lipoxgenase (Alox15), a key enzyme in this SPM biosynthesis.
The significant VNS-mediated reduction in neutrophil count in peritoneal exudates was absent in mice deficient in the α7-nicotinic acetylcholine cholinergic receptor (α7nAChR) subunit, a critical component of the inflammatory reflex.
Thus, VNS increased local SPM levels and accelerated resolution of inflammation in zymosan-induced peritonitis through a mechanism involving Alox15 and requiring α7nAChR.