Electrical vagus nerve stimulation and nicotine effects in peritonitis-induced acute lung injury in rats

Inflammation. 2011 Feb;34(1):29-35. doi: 10.1007/s10753-010-9204-5.


The cholinergic anti-inflammatory pathway has been identified as playing a key role in the communication between the central nervous system and the immune system during inflammation. The potential beneficial role of vagus nerve stimulation (VNS) remains to be clarified in established sepsis. We hypothesized that VNS or nicotine administration would reduce lung injury and mortality in established sepsis. We conducted a prospective, randomized experimental study. Four hours after peritonitis induction by cecal ligation and puncture (CLP), rats were randomized into three groups of seven animals according to the intervention: control group, VNS group (15 V, 2 ms, 5 Hz during 20 min), and nicotine group (400 µg/kg intraperitoneal). Survival was determined as lung injury score 4 and 8 h after CLP. Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, cytokine-induced neutrophil chemoattractant (CINC)-3 and thrombin-antithrombin complexes (TATc) were measured at baseline and at 4 and 8 h after CLP. Survival at 8 h was 71.4%, 100%, and 23.8% in the control, VNS, and nicotine groups, respectively (p < 0.05). All animals had lung damage but without significant difference between groups even if nicotine-treated animals tended to have a higher score than the controls (p = 0.09). Neutrophil polymorphonuclear (PMN) infiltration was more pronounced in the nicotine group compared with the VNS group (p = 0.015) but not with the controls. TNF-α, IL-6, IL-10, CINC-3, and TATc were elevated in all groups (NS). In this model of established sepsis, posttreatment by VNS was associated with increased survival, while nicotine administration increased lung PMN infiltration and mortality. Nicotine-induced bacterial clearance impairment and nicotine systemic effects may explain these observations.

MeSH terms

  • Acute Lung Injury / immunology*
  • Acute Lung Injury / pathology*
  • Animals
  • Antithrombin III
  • Cecum
  • Chemokine CXCL2 / blood
  • Electric Stimulation Therapy*
  • Inflammation / immunology
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Kaplan-Meier Estimate
  • Ligation
  • Neutrophil Infiltration / drug effects
  • Nicotine / pharmacology*
  • Peptide Hydrolases / blood
  • Peritonitis / complications
  • Peritonitis / immunology*
  • Peritonitis / pathology*
  • Rats
  • Tumor Necrosis Factor-alpha / blood
  • Vagus Nerve / physiology*


  • Chemokine CXCL2
  • Cxcl2 protein, rat
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • antithrombin III-protease complex
  • Interleukin-10
  • Nicotine
  • Antithrombin III
  • Peptide Hydrolases