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Physiology and immunology of the cholinergic antiinflammatory pathway
Kevin J. Tracey
Kevin J. Tracey
Published February 1, 2007
Citation Information: J Clin Invest. 2007;117(2):289-296. https://doi.org/10.1172/JCI30555.
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Review Article has an altmetric score of 62

Physiology and immunology of the cholinergic antiinflammatory pathway

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Abstract

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.

Authors

Kevin J. Tracey

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Figure 4

The immunological homunculus.

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The immunological homunculus.
The CNS is organized somatotopically, such...
The CNS is organized somatotopically, such that specific neural networks regulate or coordinate particular actions in the periphery. Advances in neuroimaging and neuroscience have made it possible to study this neural organization in humans. Knowledge about the cholinergic antiinflammatory pathway as a specific regulator of cytokine responses makes it possible to consider whether there is somatotopic organization to CNS regulation and coordination of the behavior of the immune system. It is plausible that this control extends beyond the simple regulation of cytokines. In the future, it may be possible to map specific brain regions that control other immune responses as depicted in this artistic rendition.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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