Summary: Electrical stimulation of the vagus nerve promotes healing in patients with acute inflammation by shifting 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 at the Karolinska Institutet in Sweden are now showing how electrical activation of a specific nerve can promote the healing of acute inflammation.
Findings that are published in the journal PNASopens new avenues for accelerating the resolution of inflammation.
The way in which the body regulates inflammation is only partially known. Previous research by Pedro Olofsson of the 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 trials of patients with inflammatory bowel disease and rheumatoid arthritis. However, it was not clear how nerve signals regulated the active management of inflammation.
“We have now studied the effects of signals between nerves and immune cells at the molecular level,” says April S. Caravaca, a researcher in Pedro Olofsson’s group at the Department of Medicine, Solna, Karolinska Institutet and Stockholm Center for Bioelectronic Medicine at MedTechLabs. .
“A better understanding of these mechanisms will allow for more accurate applications that use the nervous system to regulate inflammation.”
Researchers have shown that electrical stimulation of the vagus nerve in inflammation shifts the balance between inflammatory and specialized anti-inflammatory molecules, which promotes healing.
“Inflammation and its resolution play a key role in a number of common diseases, including autoimmune diseases and cardiovascular diseases,” says Peder Olofsson.
“Our findings provide insights 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 inflammation healing.
“The vagus nerve is just one of many nerves that regulate the immune system. We will continue to map the networks of nerves that regulate inflammation at the molecular level and study how these signals contribute to the development of the disease, ”says Dr Olofsson.
“We hope that this research will provide a better understanding of how pathological inflammation can be addressed and contribute to more effective treatment of many inflammatory diseases, such as atherosclerosis and rheumatism.”
Financing: 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 head of research at Resolomics Ltd.
About these research reports on brain stimulation and inflammation
Author: Press office
Source: Karolinska Institute
Contact: Press Department – Karolinska Institute
Picture: The image is in the public domain
Original research: Closed access.
April S. Caravaca et al .: “Stamina nerve stimulation promotes the resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit.” PNAS
Vaginal nerve stimulation promotes inflammation by a mechanism involving Alox15 and requires the α7nAChR subunit
Unresolved inflammation is the basis of many chronic inflammatory diseases, and therapeutic acceleration of the disappearance of inflammation can improve results.
Nerve reflexes regulate the intensity of inflammation (e.g., through signals in the vagus nerve), but it is not known whether activation of the vagus nerve promotes resolution of inflammation in vivo.
To investigate this, mice underwent electrical vagus nerve stimulation (VNS) or simulated cervical surgery followed by zymosan-induced peritonitis.
The duration of remission of inflammation was significantly shortened and efferocytosis was significantly increased in VNS-treated mice compared to the simulation. Lipid mediator (LM) metabololipidomics revealed that VNS-treated mice had higher levels of specialized resolving mediators (SPM), especially from omega-3 docosahexaene (DHA) and docosapentaene (n-3 DPA) metabolomas in peritoneal exudates.
VNS also shifted the ratio between pro-inflammatory and pro-resolving LMs towards a pro-resolving profile, but this effect of VNS was inverted in 12/15-lipoxgenase (Alox15) deficient mice, a key enzyme in this SPM biosynthesis.
A significant reduction in neutrophil counts in peritoneal exudates mediated by VNS was absent in mice deficient in the cholinergic α7-nicotinic acetylcholine receptor (α7nAChR) subunit, an essential component of the inflammatory reflex.
Thus, VNS increased local SPM levels and accelerated the resolution of inflammation in zymosan-induced peritonitis by a mechanism that involves Alox15 and requires α7nAChR.
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