Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

Lyudmila V. Borovikova, Svetlana Ivanova, Minghuang Zhang, Huan Yang, Galina I. Botchkina, Linda R. Watkins, Haichao Wang, Naji Abumrad, John W. Eaton and Kevin J. Tracey ()
Additional contact information
Lyudmila V. Borovikova: The Picower Institute for Medical Research
Svetlana Ivanova: The Picower Institute for Medical Research
Minghuang Zhang: The Picower Institute for Medical Research
Huan Yang: The Picower Institute for Medical Research
Galina I. Botchkina: The Picower Institute for Medical Research
Linda R. Watkins: University of Colorado
Naji Abumrad: Department of Emergency Medicine
John W. Eaton: Department of Pediatrics Baylor College of Medicine
Kevin J. Tracey: Department of Emergency Medicine

Nature, 2000, vol. 405, issue 6785, 458-462

Abstract: Abstract Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal1,2,3,4. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms5,6,7,8. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic–pituitary–adrenal anti-inflammatory responses9,10,11. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1β, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.

Date: 2000
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DOI: 10.1038/35013070

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