Vagus nerve integrity and experimental colitis

Am J Physiol Gastrointest Liver Physiol. 2007 Sep;293(3):G560-7. doi: 10.1152/ajpgi.00098.2007. Epub 2007 Jun 21.

Abstract

Previous studies have identified a counterinflammatory vagal reflex in the context of endotoxic shock. We have extended this observation to show that the vagus confers protection against acute (5 days) colitis induced by dextran sodium sulfate (DSS) or by dinitrobenzene sulfonic acid (DNBS). We have shown that this is mediated via macrophages and involves the suppression of proinflammatory cytokines. In this study, we have examined whether the vagal integrity confers long-lasting protection by studying DNBS- and DSS-induced inflammatory responses in the colon at 9 to 61 days postvagotomy. The integrity of vagotomy was confirmed at all time points using CCK-induced satiety. As previously described in a DNBS and DSS model, vagotomy associated with the pyloroplasty increased all indices of inflammation. Vagotomy increased the disease activity index as well as the macroscopic and histological scores by 75 and 41%, respectively. In addition, myeloperoxidase (MPO) activity, serum levels of C-reactive protein (CRP), and colonic tissue levels of proinflammatory cytokine increased when colitis was induced 9 days postvagotomy. However, these increases in inflammatory indices were substantially diminished in mice with colitis induced 21, 33, and 61 days postvagotomy. This was accompanied by an increased production of interleukin-10, transforming growth factor-beta, Forkhead Box P3 (FOXP3) staining in colonic tissue, and serum corticosterone. These findings indicate that although vagal integrity is an important protective factor, other counterinflammatory mechanisms come into play if vagal integrity is compromised beyond 2 wk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Reactive Protein / metabolism
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / pathology
  • Colitis / physiopathology*
  • Colon / innervation*
  • Colon / metabolism
  • Colon / pathology
  • Colon / physiopathology
  • Corticosterone / blood
  • Dextran Sulfate
  • Dinitrofluorobenzene / analogs & derivatives
  • Disease Models, Animal
  • Eating
  • Forkhead Transcription Factors / metabolism
  • Interleukins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / metabolism
  • Reflex*
  • Severity of Illness Index
  • Sincalide / metabolism
  • T-Lymphocytes, Regulatory / metabolism
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Vagotomy, Truncal
  • Vagus Nerve / physiopathology*
  • Vagus Nerve / surgery

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, rat
  • Interleukins
  • Transforming Growth Factor beta
  • 2,4-dinitrofluorobenzene sulfonic acid
  • C-Reactive Protein
  • Dextran Sulfate
  • Dinitrofluorobenzene
  • Peroxidase
  • Sincalide
  • Corticosterone