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Vagus Nerve Stimulation Emerges as Potential Treatment for Infections

Neurons sending a signal to neighbouring neurons
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The spleen is heavily involved in the body’s immune response to infections, producing and regulating antibodies. Yet, while key to helping organisms fight pathogens, an overproduction of antibodies can be detrimental.

New research from the Feinstein Institutes for Medical Research has shown that stimulation of the vagus nerve triggers activation of the spleen, thereby regulating the production of antibodies.

The researchers found that chronic vagus nerve activation by an implanted bioelectronic device suppresses the production of antibodies. These findings suggest that bioelectronic devices delivering vagus nerve stimulation (VNS) could be used in the future to control abnormal production of antibodies in conditions such as sepsis and lupus.

The study was published in the journal Science Advances.

How does the vagus nerve influence immune response?

The vagus nerve is connected to the splenic nerve, a small nerve branch that extends between a collection of neurons in the abdomen (called the celiac ganglion) and the spleen.

What is the vagus nerve?

The vagus nerve is one the main nerves that form the parasympathetic nervous system, often nicknamed the “rest and digest” system. The nerve plays important roles in involuntary sensory and motor functions such as heart rate, respiration, immune response and digestion.

“Stimulation of the vagus nerve activates the splenic nerve which releases small amounts of neurotransmitters in the spleen. These chemicals bind to immune cells present inside the spleen, altering many of their immune-related functions,” Dr. Stavros Zanos, associate professor at the Feinstein Institutes for Medical Research, told Technology Networks.

“This pathway, from the vagus nerve to the immune cells of the spleen, is part of the ‘inflammatory reflex’, a neural circuit that regulates immunity and includes neurons in areas of the brain.”

The researchers found that acetylcholine released in response to VNS interacts with specific receptors on the surface of splenic B cells, thereby altering their ability to produce signaling molecules and mature. This results in a decrease in the production of specific antibodies.

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An improved understanding of the specific receptors and molecular pathways in B cells by which the vagus nerve exerts a suppressive action could provide possible new drug targets.

Bioelectronic medicine: A promising alternative to immune-modulating drugs

The researchers suggest an implanted bioelectronic device to simulate VNS could be a viable treatment option for diseases involving adaptive immunity. Implantation of a vagus nerve stimulator is a relatively simple and safe surgical procedure that is Food and Drug Administration (FDA) approved for treating patients with certain types of epilepsy.

Discussing the potential benefits of a vagus nerve stimulator implant for treating autoimmune diseases, Zanos said “VNS essentially makes use of naturally existing mechanisms for controlling exaggerated immune activation in sepsis (and in other diseases) and, for that reason, it does not produce some of the serious side-effects of traditional immune-modulating medications.”

“If VNS is successful, it would be a ‘get-and-forget’ solution, since patients would not need to follow instructions for daily medications, thereby simplifying therapy and helping with patient compliance. It would also be a much cheaper treatment option than long-term, sometimes lifelong, administration of immune-modulating medications.”

Discussing future studies, Zanos points to the need for further research in preclinical models to determine the potential of VNS in alleviating the severity of diseases such as sepsis. Another avenue of future research will be looking to see if altered levels of specific antibodies or molecules involved in specific B-cell functions could be used as biomarkers of the activation of the inflammatory reflex and of disease severity.

Zanos concluded: “There are many open questions that need to be addressed. For example, what is the level of "natural" activity of the inflammatory reflex in conditions like sepsis and lupus, and whether VNS could ameliorate the severity of these diseases.”

Dr. Stavros Zanos was speaking to Blake Forman, Senior Science Writer and Editor for Technology Networks.

About the interviewee:

Dr. Stavros Zanos is an associate professor in the Institute of Bioelectronic Medicine at the Feinstein Institutes for Medical Research. Zanos obtained his MD from Aristotle University and earned a PhD in neuroscience and physiology from the University of Washington. His research is focused on neurostimulation as a means to study the nervous system and to treat diseases in which the nervous system is affected or implicated.

Reference: Kurata-Sato I, Mughrabi IT, Rana M, et al. Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response. Sci Adv. 2024;10(17):eadn3760. doi: 10.1126/sciadv.adn3760