Activation of cholinergic anti-inflammatory pathway contributes to the protective effects of 100% oxygen inhalation on zymosan-induced generalized inflammation in mice

J Surg Res. 2012 May 15;174(2):e75-83. doi: 10.1016/j.jss.2011.10.037. Epub 2011 Nov 21.

Abstract

Background: The 100% oxygen inhalation has been demonstrated to have a protective effect on mice with zymosan-induced generalized inflammation. However, the underlying mechanism is largely unknown. The present study was designed to explore the role of the cholinergic anti-inflammatory pathway in this animal model.

Methods: Oxygen inhalation was given to mice at 4 and 12 h after zymosan injection. One group of mice underwent vagotomy 7 d before zymosan injection. The other two groups of mice either received nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine, or α7 nicotinic acetylcholine receptor (α7nAChR) antagonist methyllycaconitine 30 min before oxygen was given.

Results: The 100% oxygen treatment significantly decreased the serum level of TNF-α and increased the serum level of IL-10. The pathologic changes of the heart, lung, liver, and kidney were attenuated, as well as the dysfunction of liver and kidney. The 7-d survival rate of zymosan-challenged mice was also improved. Conversely, all these protective effects caused by pure oxygen treatment were abolished in those animals that received anti-cholinergic treatments.

Conclusions: The cholinergic anti-inflammatory pathway may be involved in the 100% oxygen protective mechanism against zymosan-induced generalized inflammation in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitine / analogs & derivatives
  • Animals
  • Cytokines / blood
  • Kidney / pathology
  • Kidney Function Tests
  • Liver / pathology
  • Liver Function Tests
  • Lung / pathology
  • Male
  • Mecamylamine
  • Mice
  • Mice, Inbred ICR
  • Myocardium / pathology
  • Nicotinic Antagonists*
  • Oxygen / therapeutic use*
  • Receptors, Nicotinic / physiology*
  • Respiratory Insufficiency / prevention & control
  • Systemic Inflammatory Response Syndrome / therapy*
  • Vagotomy*
  • Zymosan

Substances

  • Cytokines
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • methyllycaconitine
  • Mecamylamine
  • Zymosan
  • Oxygen
  • Aconitine