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 sub-anesthetic doses and its effects upon 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 ketamine (70, 7, or 1 mg/kg IP) or saline one hour before LPS (20 mg/kg IP) or saline. Five hours after LPS, rats were sacrificed. Serum was collected for cytokine analysis. In other experiments, male rats were given ketamine (7 mg/kg IP) or saline one hour prior to induction of TBI with controlled cortical impact (or sham). One and six hours following injury, brain was extracted for analysis of cerebral edema and cytokine production. Results LPS increased the serum concentrations of IL-1α, IL-1β, IL-6, IL-10, TNF-α, and IFN-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 TNF-α. However, ketamine had minimal effect on TBI induced inflammation. Conclusions While ketamine did not appear 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.

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