Fig. 1

The inflammatory reflex. In the inflammatory reflex, the activity of afferent vagus nerve fibers residing in the nodose ganglion is stimulated by cytokines and pathogen-associated molecular patterns (PAMPs). The signal is transmitted to the NTS. Reciprocal connections between the NTS and DMN mediate communication with and activation of efferent vagus nerve fibers from the DMN. The signal is propagated to the celiac ganglia and the superior mesenteric ganglion in the celiac plexus, where the splenic nerve originates. Norepinephrine (NE) released from the splenic nerve interacts with β₂-adrenergic receptors (β₂-ARs) and causes the release of acetylcholine (ACh) from T cells containing functional choline acetyltransferase (T-ChAT cells). ACh interacts with α7nAChRs on macrophages and suppresses proinflammatory cytokine release and inflammation. The inflammatory reflex can be activated through brain mAChR-mediated mechanisms by centrally-acting M1 mAChR agonists and acetylcholinesterase (AChE) inhibitors. Somatosensory activation by electroacupuncture at the Hegu point also causes activation of brain mAChR signaling, which then results in activation of efferent vagus and splenic anti-inflammatory signaling. Electroacupuncture at a different acupuncture point activates sciatic nerve signals, which by unknown mechanisms convert to efferent vagus nerve signaling to the adrenal medulla, resulting in dopamine release. Dopamine suppresses inflammation and improves survival in a model of sepsis. Vagus nerve and splenic nerve signaling mediated through α7nAChR on splenocytes controls inflammation in acute kidney injury and alleviates the condition. (Figure created by Debbie Maizels, Springer Nature, for Pavlov and Tracey 2017; reprinted, with permission, from the authors in conjunction with Springer Nature)