Ketamine improves survival and suppresses IL-6 and TNFalpha production in a model of Gram-negative bacterial sepsis in rats

Objective: In a previous study, ketamine suppressed Escherichia coli-induced production of the cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNFα). In other previous studies ketamine improved survival after E. coli inoculation. However, the relationship between cytokines and survival following ketamine treatment is uncertain because no study has examined both cytokines and survival after E. coli inoculation. Methods: Rats were given E. coli (0.4×10⁹ colony forming unit (CFU)) at time 0, followed by ketamine (50 mg/kg, n=30) or saline (n=30) at 5 min or 2 h. IL-6 and TNFα were measured in serum at 6 h, and mortality was recorded for 7 days. Results: Survival rate with ketamine was 57% (17/30) and was significantly increased compared to saline (27%, 8/30, P=0.01). IL-6 and TNFα were lower with ketamine than saline (15,197±3444 versus 30,725±4623 pg/ml [mean±S.E.M.], P=0.013 and 38.5±9.5 versus 122.5±14.0 pg/ml, P=0.001, respectively). With ketamine, IL-6 (but not TNFα) concentrations were lower in the survivors (10,900±776 pg/ml) as compared to the non-survivors (P=0.01). IL-6 in ketamine-treated survivors was not different from that in saline-treated survivors. Conclusion: We conclude that ketamine given 5 min or 2 h after induction of E. coli sepsis significantly improves survival, possibly by interfering with the inflammatory cascade (as evidenced by attenuation of cytokine production).