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

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

Research output: Contribution to journalArticle

259 Citations (Scopus)

Abstract

Background & Aims: The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-α 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 α7 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 α7 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.

Original languageEnglish (US)
Pages (from-to)1822-1830
Number of pages9
JournalGastroenterology
Volume130
Issue number6
DOIs
StatePublished - Jun 2006

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Vagus Nerve
Nicotinic Receptors
Pancreatitis
Mecamylamine
Anti-Inflammatory Agents
Vagotomy
Neutrophils
Macrophages
Nicotinic Agonists
Nicotinic Antagonists
Inflammation
Ceruletide
Cholinergic Receptors
Hydrolases
Intraperitoneal Injections
Endotoxins
Nervous System
Peroxidase
Acetylcholine
Neurotransmitter Agents

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

van Westerloo, D. J., Giebelen, I. A., Florquin, S., Bruno, M. J., LaRosa, G. J., Ulloa, L., ... van der Poll, T. (2006). The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice. Gastroenterology, 130(6), 1822-1830. https://doi.org/10.1053/j.gastro.2006.02.022
van Westerloo, David J. ; Giebelen, Ilona A. ; Florquin, Sandrine ; Bruno, Marco J. ; LaRosa, Gregory J. ; Ulloa, Luis ; Tracey, Kevin J. ; van der Poll, T. / The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice. In: Gastroenterology. 2006 ; Vol. 130, No. 6. pp. 1822-1830.
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van Westerloo, DJ, Giebelen, IA, Florquin, S, Bruno, MJ, LaRosa, GJ, Ulloa, L, Tracey, KJ & van der Poll, T 2006, 'The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice', Gastroenterology, vol. 130, no. 6, pp. 1822-1830. https://doi.org/10.1053/j.gastro.2006.02.022

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.

In: Gastroenterology, Vol. 130, No. 6, 06.2006, p. 1822-1830.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice

AU - van Westerloo, David J.

AU - Giebelen, Ilona A.

AU - Florquin, Sandrine

AU - Bruno, Marco J.

AU - LaRosa, Gregory J.

AU - Ulloa, Luis

AU - Tracey, Kevin J.

AU - van der Poll, T.

PY - 2006/6

Y1 - 2006/6

N2 - Background & Aims: The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-α 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 α7 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 α7 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.

AB - Background & Aims: The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-α 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 α7 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 α7 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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