Schematic representation of the cholinergic antiinflammatory pathway. The reflex is activated in the circumventricular brainstem and vagal afferent fibers through signaling by inflammatory mediators. After integration, this sensory input will trigger the efferent arm via the celiac ganglion, modulating the immune response in the spleen. Adrenergic neurons in the spleen release norepinephrine that induces acetylcholine release by a subset of splenic T cells. Acetylcholine ligands the α7nAChR expressed on cytokine-producing macrophages thereby reducing the release of TNF, IL-1, IL-18, HMGB1, and other cytokines. During intestinal inflammation the vagal efferent fibers directly contact myenteric neurons in the intestinal wall. Enteric neurons release acetylcholine, similarly reducing intestinal macrophage cytokine release. Image from (14) (reproduced from Gut, The vagal innervation of the gut and immune homeostasis, Gianluca Matteoli, Guy E Boeckxstaens, 62:1214-22, © 2013, with permission from BMJ Publishing Group Ltd.).