title: Effects of ketamine on endotoxin and traumatic brain injury induced cytokine production in the rat.
abstract: BACKGROUND
  Endotoxemia from lipopolysaccharide (LPS) induces systemic cytokine production, whereas traumatic brain injury (TBI) increases intracerebral cytokine production. In anesthetic doses, ketamine has potent anti-inflammatory properties. However, its anti-inflammatory effects at subanesthetic doses and its effects on TBI-induced inflammation have not been fully investigated. We hypothesized that ketamine would attenuate both LPS- and TBI-induced inflammatory responses.
  
  
  METHODS
  Male rats received intraperitoneal (i.p.) ketamine (70 mg/kg, 7 mg/kg, or 1 mg/kg) or saline 1 hour before LPS (20 mg/kg i.p.) or saline. Five hours after LPS, rats were killed. Serum was collected for cytokine analysis. In other experiments, male rats were given ketamine (7 mg/kg i.p.) or saline 1 hour before induction of TBI with controlled cortical impact (or sham). One hour and 6 hours after injury, brain was extracted for analysis of cerebral edema and cytokine production.
  
  
  RESULTS
  LPS increased the serum concentrations of interleukin (IL)-1α, IL-1β, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ. Ketamine dose dependently attenuated these changes. TBI caused cerebral edema and increased concentrations of cerebral IL-1α, IL-1β, IL-6, IL-10, and tumor necrosis factor-α. However, ketamine had minimal effect on TBI-induced inflammation.
  
  
  CONCLUSIONS
  Although ketamine did not seem to exert any beneficial effects against TBI in the rat, it did not exacerbate cytokine production or enhance cerebral edema as some studies have suggested.
authors.affiliation: Department of Surgery, New York University Langone Medical Center, New York, New York 10016, USA. jeremy.ward@nyumc.org
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Ward
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Harting
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cox
authors.forename: David W
authors.initials: DW
authors.lastname: Mercer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy*; D001930:Brain Injuries / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D007649:Ketamine