Inflammation and other immune responses are involved in thevariety of diseases and disorders. The acute response toendotoxemia includes activation of innate immune mechanismsas well as changes in autonomic nervous activity. The autonomicnervous system and the inflammatory response are intimatelylinked and sympathetic and vagal nerves are thought to haveanti-inflammation functions. The basic functional circuit betweenvagus nerve and inflammatory response was identified and theneuroimmunomodulation loop was called cholinergicanti-inflammatory pathway. Unique function of vagus nerve inthe anti-inflammatory reflex arc was found in many experimentaland pre-clinical studies. They brought evidence on the cholinergicsignaling interacting with systemic and local inflammation,particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-α andother proinflammatory cytokines production and had beneficialtherapeutic effects. Many questions related to mapping, linkingand targeting of vagal-immune interactions have been elucidatedand brought understanding of its basic physiology and providedthe initial support for development of Tracey′s inflammatoryreflex. This review summarizes and critically assesses the currentknowledge defining cholinergic anti-inflammatory pathway withmain focus on studies employing an experimental approach andemphasizes the potential of modulation of vagally-mediatedanti-inflammatory pathway in the treatment strategies.
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