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Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin.
Nature. 2000 May 25; 405(6785):458-62.Nat

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 lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. 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)-1beta, 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.

Authors+Show Affiliations

The Picower Institute for Medical Research, Manhasset, New York 11030, USA. lborovikova@mindspring.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10839541

Citation

Borovikova, L V., et al. "Vagus Nerve Stimulation Attenuates the Systemic Inflammatory Response to Endotoxin." Nature, vol. 405, no. 6785, 2000, pp. 458-62.
Borovikova LV, Ivanova S, Zhang M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405(6785):458-62.
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., Wang, H., Abumrad, N., Eaton, J. W., & Tracey, K. J. (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 405(6785), 458-62.
Borovikova LV, et al. Vagus Nerve Stimulation Attenuates the Systemic Inflammatory Response to Endotoxin. Nature. 2000 May 25;405(6785):458-62. PubMed PMID: 10839541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. AU - Borovikova,L V, AU - Ivanova,S, AU - Zhang,M, AU - Yang,H, AU - Botchkina,G I, AU - Watkins,L R, AU - Wang,H, AU - Abumrad,N, AU - Eaton,J W, AU - Tracey,K J, PY - 2000/6/6/pubmed PY - 2000/6/24/medline PY - 2000/6/6/entrez SP - 458 EP - 62 JF - Nature JO - Nature VL - 405 IS - 6785 N2 - 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 lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. 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)-1beta, 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. SN - 0028-0836 UR - https://www.unboundmedicine.com/medline/citation/10839541/Vagus_nerve_stimulation_attenuates_the_systemic_inflammatory_response_to_endotoxin_ L2 - https://doi.org/10.1038/35013070 DB - PRIME DP - Unbound Medicine ER -