The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice
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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A pharmacological approach to therapy may be useful even when the basal activity of the vagus nerve during pancreatitis is insufficient to suppress cytokines.
“This occurred even when the vagus nerves had been cut, indicating that a pharmacological approach to therapy may be useful even when the basal activity of the vagus nerve during the disease is insufficient to suppress cytokines.”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [24]
Administration of GTS-21 significantly decreases pancreatitis severity and attenuates pulmonary inflammation.
“Administration of GTS-21, an α7 nAChR receptor agonist, significantly decreased pancreati-tis severity and attenuated pulmonary inflammation (24).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [24]
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Self-citation
- 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)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 130
- Issue
- 6
- Pages
- 1822-1830
- ISSN
- 0016-5085 (ISSN-L)
- 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
- 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 › Surgery › 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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