Science, Medicine, and the Anesthesiologist

Previous work has shown the significance of electrical stimulation of the vagal nerve to attenuate inflammation. To decipher how the brain regulates the body’s immune response, activities of neurons in the brain stems of mice were monitored after infliction of a peripheral immune insult by intraperitoneal injection of endotoxin (lipopolysaccharide). Activation of c-fos, a proxy for neuronal activity, was strong in the caudal nucleus of the solitary tract (cNST). Lipopolysaccharide-evoked neural activity in the cNST was blocked by subdiaphragmatic transection of the vagus nerve. Chemogenetic activation and inhibition of lipopolysaccharide-sensitive cNST neurons, single-cell RNA sequencing, and functional imaging were used to identify the components of the interaction between immune system and the brain. Activation of lipopolysaccharide-sensitive cNST neurons reduced the proinflammatory response by 70% and increased the anti-inflammatory response 10-fold, while their inhibition dramatically increased the proinflammatory response by 300%. Additional experiments showed that specific vagal nerve fibers, mainly from the small intestine, were activated by cytokines and transmitted the inflammatory signal to cNST neurons. The significance of this body–brain circuit could be demonstrated in mice where this circuit had been activated chemogenetically and subsequently injected with lethal doses of lipopolysaccharide, resulting in an astonishing survival rate of 90%.

Take home message: Pharmacologically targeting cNST neurons may provide a powerful treatment of hyperactive immune states such as autoimmune diseases, cytokine storms, and toxic shocks.