Physiology and immunology of the cholinergic antiinflammatory pathway

J Clin Invest. 2007 Feb;117(2):289-96. doi: 10.1172/JCI30555.


Cytokine production by the immune system contributes importantly to both health and disease. The nervous system, via an inflammatory reflex of the vagus nerve, can inhibit cytokine release and thereby prevent tissue injury and death. The efferent neural signaling pathway is termed the cholinergic antiinflammatory pathway. Cholinergic agonists inhibit cytokine synthesis and protect against cytokine-mediated diseases. Stimulation of the vagus nerve prevents the damaging effects of cytokine release in experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, arthritis, and other inflammatory syndromes. Herein is a review of this physiological, functional anatomical mechanism for neurological regulation of cytokine-dependent disease that begins to define an immunological homunculus.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / physiology
  • Cholinergic Fibers / immunology*
  • Cholinergic Fibers / physiology*
  • Cytokines / history
  • Cytokines / immunology
  • Cytokines / physiology
  • History, 20th Century
  • History, 21st Century
  • History, Ancient
  • Humans
  • Inflammation / immunology*
  • Inflammation / physiopathology*
  • Inflammation / therapy
  • Models, Biological


  • Cytokines