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The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis.
J Infect Dis. 2005 Jun 15; 191(12):2138-48.JI

Abstract

BACKGROUND

The nervous system, through the vagus nerve, can down-regulate inflammation in vivo by decreasing the release of tumor necrosis factor- alpha by endotoxin-stimulated macrophages. This anti-inflammatory effect is mediated by an interaction between acetylcholine, the principal neurotransmitter of the vagus nerve, and cholinergic nicotinic acetylcholine receptors on macrophages.

METHODS

We determined the role of this "cholinergic anti-inflammatory pathway" during septic peritonitis induced in mice by intraperitoneal injection of live Escherichia coli. Septic peritonitis was preceded by inhibition of the cholinergic anti-inflammatory pathway by unilateral cervical vagotomy, by stimulation of this pathway by pretreatment of mice with nicotine, or by a combination of both interventions.

RESULTS

Initial cytokine release during septic peritonitis was enhanced after previous vagotomy and was decreased after nicotine pretreatment, independently of the integrity of the vagus nerve. Further study established that vagotomy before septic peritonitis resulted in an enhanced influx of neutrophils and a marked increase in proinflammatory cytokine levels and liver damage. Conversely, nicotine pretreatment strongly decreased cell influx, proinflammatory cytokine levels, and liver damage, whereas bacterial clearance and survival were impaired.

DISCUSSION

These data provide the first evidence, to our knowledge, of an important role of the vagus nerve in regulating the innate immune response to a severe bacterial infection.

Authors+Show Affiliations

Laboratory of Experimental Internal Medicine and Department of Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. d.j.vanwesterloo@amc.uva.nlNo 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15898001

Citation

van Westerloo, David J., et al. "The Cholinergic Anti-inflammatory Pathway Regulates the Host Response During Septic Peritonitis." The Journal of Infectious Diseases, vol. 191, no. 12, 2005, pp. 2138-48.
van Westerloo DJ, Giebelen IA, Florquin S, et al. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis. 2005;191(12):2138-48.
van Westerloo, D. J., Giebelen, I. A., Florquin, S., Daalhuisen, J., Bruno, M. J., de Vos, A. F., Tracey, K. J., & van der Poll, T. (2005). The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. The Journal of Infectious Diseases, 191(12), 2138-48.
van Westerloo DJ, et al. The Cholinergic Anti-inflammatory Pathway Regulates the Host Response During Septic Peritonitis. J Infect Dis. 2005 Jun 15;191(12):2138-48. PubMed PMID: 15898001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. AU - van Westerloo,David J, AU - Giebelen,Ilona A J, AU - Florquin,Sandrine, AU - Daalhuisen,Joost, AU - Bruno,Marco J, AU - de Vos,Alex F, AU - Tracey,Kevin J, AU - van der Poll,Tom, Y1 - 2005/05/10/ PY - 2004/10/05/received PY - 2005/01/15/accepted PY - 2005/5/18/pubmed PY - 2005/7/29/medline PY - 2005/5/18/entrez SP - 2138 EP - 48 JF - The Journal of infectious diseases JO - J Infect Dis VL - 191 IS - 12 N2 - BACKGROUND: The nervous system, through the vagus nerve, can down-regulate inflammation in vivo by decreasing the release of tumor necrosis factor- alpha by endotoxin-stimulated macrophages. This anti-inflammatory effect is mediated by an interaction between acetylcholine, the principal neurotransmitter of the vagus nerve, and cholinergic nicotinic acetylcholine receptors on macrophages. METHODS: We determined the role of this "cholinergic anti-inflammatory pathway" during septic peritonitis induced in mice by intraperitoneal injection of live Escherichia coli. Septic peritonitis was preceded by inhibition of the cholinergic anti-inflammatory pathway by unilateral cervical vagotomy, by stimulation of this pathway by pretreatment of mice with nicotine, or by a combination of both interventions. RESULTS: Initial cytokine release during septic peritonitis was enhanced after previous vagotomy and was decreased after nicotine pretreatment, independently of the integrity of the vagus nerve. Further study established that vagotomy before septic peritonitis resulted in an enhanced influx of neutrophils and a marked increase in proinflammatory cytokine levels and liver damage. Conversely, nicotine pretreatment strongly decreased cell influx, proinflammatory cytokine levels, and liver damage, whereas bacterial clearance and survival were impaired. DISCUSSION: These data provide the first evidence, to our knowledge, of an important role of the vagus nerve in regulating the innate immune response to a severe bacterial infection. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/15898001/The_cholinergic_anti_inflammatory_pathway_regulates_the_host_response_during_septic_peritonitis_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/430323 DB - PRIME DP - Unbound Medicine ER -