The Role of the Vagus Nerve: Modulation of the Inflammatory Reaction in Murine Polymicrobial Sepsis

Abstract

The particular importance of the vagus nerve for the pathophysiology of peritonitis becomes more and more apparent. In this work we provide evidence for the vagal modulation of inflammation in the murine model of colon ascendens stent peritonitis (CASP). Vagotomy significantly increases mortality in polymicrobial sepsis. This effect is not accounted for by the dilatation of gastric volume following vagotomy. As the stimulation of cholinergic receptors by nicotine has no therapeutic effect, the lack of nicotine is also not the reason for the reduced survival rate. In fact, increased septic mortality is a consequence of the absent modulating influence of the vagus nerve on the immune system: we detected significantly elevated serum corticosterone levels in vagotomised mice 24 h following CASP and a decreased ex vivo TNF-alpha secretion of Kupffer cells upon stimulation with LPS. In conclusion, the vagus nerve has a modulating influence in polymicrobial sepsis by attenuating the immune dysregulation.

Successful treatment of severe sepsis and diarrhea after vagotomy utilizing fecal microbiota transplantation: a case report

“…Recently, the vagal innervation of the gastrointestinal tract has been proposed to be involved in the regulation of the inflammatory response in animal models of sepsis [ 30 , 31 ]. Vagotomies are frequently performed in patients with gastrectomy.…”

Relationship between clinical features and inflammation‐related monocyte gene expression in bipolar disorder – towards a better understanding of psychoimmunological interactions

“…Indeed, the vagus nerve is known to be essential for balancing anti‐ and pro‐inflammatory mechanisms during sepsis . There have been multiple observations of mania following vagus nerve stimulation, a treatment for refractory epilepsy thought to have its effect on the limbic system and frontal cortex .…”

Effect of GTS-21, an Alpha7 Nicotinic Acetylcholine Receptor Agonist, on CLP-Induced Inflammatory, Gastrointestinal Motility, and Colonic Permeability Changes in Mice

“…GTS-21, a selective partial a7nAChR agonist currently under investigation for its neuroprotective effects, has been demonstrated to suppress inflammation in various animal models of inflammation, such as acute kidney injury (9), pancreatitis (10), and ventilator-induced injury (11). Animal studies have already demonstrated the beneficial effects of vagal nerve stimulation (VNS) on survival following LPS-induced murine sepsis (12), whereas mortality was increased following vagotomy in the colon ascendens stent peritonitis animal model (13). These beneficial effects were demonstrated to be dependent on the presence of an intact vagus-nerve to spleen neuronal circuit (14,15).…”