title: Anti-inflammatory effects of sevoflurane and mild hypothermia in endotoxemic rats.
abstract: BACKGROUND
  Volatile anesthetics and hypothermia attenuate the inflammatory response. We aimed to compare the anti-inflammatory effects of sevoflurane and mild hypothermia during experimental endotoxemia in the rat.
  
  
  METHODS
  Anesthetized, ventilated Sprague-Dawley (SD) rats were randomly treated as follows (n = 6 per group): lipopolysaccharide (LPS) only, animals received LPS [LPS 5 mg/kg, intravenously (i.v.)] with no further treatment. In the LPS-hypothermia group, rats were cooled down to a temperature of 33 degrees C 15 min after LPS-injection (LPS 5 mg/kg i.v.). In animals of the LPS-sevoflurane group, sevoflurane inhalation (1 MAC) was initiated 15 min after induction of endotoxemia. The LPS-sevoflurane-hypothermia group received combined sevoflurane and hypothermia 15 min after induction of endotoxemia. A Sham group served as control without endotoxemia or treatment. After 4 h of endotoxemia, plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-10 were measured. Alveolar macrophages (AM) were ex vivo cultured for nitrite assay.
  
  
  RESULTS
  Inhalation of sevoflurane significantly attenuated plasma levels of TNF-alpha (-60%, P < 0.05) and IL-1beta (-68%, P < 0.05) as compared with the LPS-only group. Hypothermia and its combination with sevoflurane significantly reduced TNF-alpha levels (-46% and -58%, each P < 0.05), but not IL-1beta. Application of mild hypothermia and also its combination with sevoflurane resulted in a significant increase in plasma IL-10 as compared with endotoxemic controls. Nitrite release from AM was found to be significantly suppressed by sevoflurane (-83%), hypothermia (-73%) and by the combination of both (-67%) (P < 0.05, each).
  
  
  CONCLUSIONS
  Our data suggest that sevoflurane and mild hypothermia attenuate the inflammatory response during endotoxemia in vivo thus contributing to their beneficial role in clinical organ protection.
authors.affiliation: Clinic for Anesthesiology, Intensive Care Medicine and Pain Therapy, Johann Wolfgang Goethe-University of Frankfurt, Frankfurt, Germany. c.hofstetter@em.uni-frankfurt.de
authors.forename: C
authors.initials: C
authors.lastname: Hofstetter
authors.forename: K A
authors.initials: KA
authors.lastname: Boost
authors.forename: M
authors.initials: M
authors.lastname: Flondor
authors.forename: E
authors.initials: E
authors.lastname: Basagan-Mogol
authors.forename: C
authors.initials: C
authors.lastname: Betz
authors.forename: M
authors.initials: M
authors.lastname: Homann
authors.forename: H
authors.initials: H
authors.lastname: Muhl
authors.forename: J
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: B
authors.initials: B
authors.lastname: Zwissler
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019446:Endotoxemia / Q000473:pathology*; D007036:Hypothermia, Induced; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008738:Methyl Ethers; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D000077149:Sevoflurane