Effects of ketamine on endotoxin and traumatic brain injury induced cytokine production in the rat

Jeremy L. Ward, Matthew T. Harting, Charles S. Cox, David W. Mercer

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1471-1479
Number of pages9
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume70
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • Cerebral edema
  • Cytokine
  • Ketamine
  • Lipopolysaccharide
  • Traumatic brain injury

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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