Cited by 378Vagus Nerve Stimulation ResearchPancreatitis Pathology and TreatmentPancreatic function and diabetes

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The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice

van Westerloo, David J., Giebelen, Ilona A., Florquin, Sandrine, Bruno, Marco J., LaRosa, Gregory J., Ulloa, Luis, Tracey, Kevin J., van der Poll, T.·2006·Gastroenterology

DOI 10.1053/j.gastro.2006.02.022

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Abstract

Background & aims The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-alpha from endotoxin stimulated macrophages. This anti-inflammatory effect is mediated by an interaction of acetylcholine, the principal neurotransmitter of the vagus nerve, with macrophage cholinergic nicotinic receptors expressing the alpha7 subunit.Methods To determine the role of this "nicotinic anti-inflammatory pathway" in experimental pancreatitis, we induced pancreatitis in mice by 12 hourly intraperitoneal injections of cerulein. Pancreatitis was preceded by unilateral left cervical vagotomy or pretreatment with the nicotinic receptor antagonist mecamylamine or by pretreatment with the selective alpha7 nicotinic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21).Results Vagotomy or pretreatment with mecamylamine resulted in an enhanced severity of pancreatitis, as reflected by histology, edema, plasma hydrolases, and interleukin-6 levels. Furthermore, the number of neutrophils migrated to the pancreas was increased in these mice, as shown by myeloperoxidase content and intrapancreatic staining of neutrophils. Conversely, GTS-21 pretreatment strongly decreased the severity of pancreatitis. Pancreatitis-associated pulmonary inflammation was independent of the integrity of the vagus nerve and nicotinic receptors.Conclusions This study provides the first evidence for a therapeutic potential of the vagus nerve and the "nicotinic anti-inflammatory pathway" in attenuating inflammation and injury during experimental pancreatitis.

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Authors: van Westerloo, D. J., Giebelen, I. A., Florquin, S., Bruno, M. J., LaRosa, G. J., Ulloa, L., Tracey, K. J., & van der Poll, T.
Affiliations: Amsterdam UMC Location University of Amsterdam (NL)
ORCID: Florquin, Sandrine
Bruno, Marco J.
Ulloa, Luis
Tracey, Kevin J.
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2006-05
Volume: 130
Issue: 6
Pages: 1822-1830
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2006.02.022
OpenAlex: W2156897641
Cited by: 377
References: 37
Citations by year: 2026: 4 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 24 · 2021: 20 · 2020: 26 · 2019: 9 · 2018: 20 · 2017: 18 · 2016: 18 · 2015: 18 · 2014: 23 · 2013: 26 · 2012: 23
FWCI: 19.09
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Funders: National Institute of General Medical Sciences (R01GM084125, R01GM057226)
Topics: Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: vagus nerve, nicotinic acetylcholine receptors, alpha7 nicotinic acetylcholine receptor, experimental pancreatitis, cerulein-induced pancreatitis, vagotomy, mecamylamine, GTS-21, cholinergic anti-inflammatory pathway, neutrophil migration, interleukin-6, lung inflammation, pancreatitis severity
MeSH terms: Animals, Biopsy, Needle, Ceruletide, Disease Models, Animal, Female, Immunohistochemistry, Mice, Inbred C57BL, Pancreatitis, Probability, Receptors, Nicotinic, Risk Factors, Sensitivity and Specificity, Severity of Illness Index, Vagotomy, Vagus Nerve, Nicotinic Antagonists, Mice

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The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice

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