title: Anesthesia-specific protection from endotoxic shock is not mediated through the vagus nerve.
abstract: BACKGROUND
  We have shown recently that volatile anesthetics significantly decrease inflammatory cytokine production and dramatically increase survival among rodents challenged with lipopolysaccharide (LPS). Because acetylcholine's interaction with nicotine receptors on tissue macrophages during vagus nerve stimulation has been implicated in the modulation of LPS-stimulated tumor necrosis factor alpha (TNF-alpha) production, we hypothesized that the mechanism of anesthetic immunoprotection is mediated through the vagus nerve.
  
  
  METHODS
  Male Sprague-Dawley rats underwent bilateral cervical vagotomy (n = 20) or sham operation (n = 6). Twenty-four hours postoperatively, vagotomized rats were randomized into 3 groups: LPS injection (V+LPS, n = 6), LPS injection followed by 60 minutes of isoflurane anesthesia (V+LPS+ISO, n = 7), or saline injection (V+S, n = 7). Sham animals were also given LPS (Sham+LPS). A sublethal dose of LPS (8 mg/kg) was used. Blood samples were collected via cardiac puncture 90 minutes after LPS or saline injection, and plasma was isolated for the measurement of cytokines by enzyme-linked immunosorbent assay. Statistical differences between groups were detected by 1-way analysis of variance.
  
  
  RESULTS
  Serum TNF-alpha was reduced significantly and interleukin (IL)-6 was abrogated completely among V+LPS+ISO rats, compared with both V+LPS and Sham+LPS animals (P < or = .05 for all). In contrast, levels of the anti-inflammatory cytokine IL-10 were similar among all LPS groups.
  
  
  CONCLUSIONS
  Isoflurane anesthesia administered simultaneously with the injection of LPS decreases serum production of TNF-alpha and IL-6 despite bilateral transection of the vagus nerve. Isoflurane-mediated attenuation of proinflammatory cytokine production occurs via a mechanism other than modulation of vagal output.
authors.affiliation: The Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Fuentes
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hanly
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Aurora
authors.forename: Antonio
authors.initials: A
authors.lastname: De Maio
authors.forename: Mark A
authors.initials: MA
authors.lastname: Talamini
mesh_terms: D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D007267:Injections; D015850:Interleukin-6 / Q000097:blood; D007530:Isoflurane / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D009333:Neck / Q000294:innervation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000503:physiopathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000503:physiopathology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D018685:Anesthetics, Inhalation; D015850:Interleukin-6; D007530:Isoflurane; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors