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Annals of Clinical & Laboratory Science 32:292-298 (2002)
© 2002 Association of Clinical Scientists

Ketamine Reduces NF{kappa}B Activation and TNF{alpha} Production in Rat Mononuclear Cells Induced by Lipopolysaccharide In Vitro

Yingqun Yu1, Zhiqiang Zhou1, Jianguo Xu1, Zhihai Liu2 and Yu Wang3
1 Departments of Anesthesiology, 2 Surgery, and 3 Pharmacology, Jinling Hospital and Nanjing University School of Medicine, Nanjing, China

Address correspondence to Jianguo Xu, M.D., Department of Anesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China; tel 86 25 482 7974; fax 86 25 361 1675; Email: xujguo{at}publicl.ptt.js.cn

Ketamine may be advantageous for anesthesia of patients with sepsis caused by gram-negative bacteria, because ketamine may suppress LPS-induced production of proinflammatory cytokines, such as TNF{alpha} and IL-6. NF{kappa}B is an important transcription factor that is involved in the post-transcriptional regulation of mRNA expression for several immunoinflammatory mediators in response to endotoxemia. This study examined the effect of ketamine on NF{kappa}B activation and TNF{alpha} production in rat peripheral blood mononuclear cells (PBMC). The PBMC were incubated in the presence or absence of LPS and with graded concentrations of ketamine. The culture supernatants and cells were collected for each group and duration of incubation. Activation of NF{kappa}B was determined by electrophoretic mobility shift assay (EMSA), and the expression of I{kappa}B{alpha}, its inhibitor, in PBMC was analysed by Western blotting. TNF{alpha} levels in the supernatants were measured using a specific enzyme-linked immunosorbent assay (ELISA). LPS stimulation of rat PBMC increased TNF{alpha} production and NF{kappa}B activation, with corresponding loss of I{kappa}B{alpha}. Ketamine significantly reduced the LPS-induced NF{kappa}B activation and inhibited TNF{alpha} production in a dose-dependent manner. These in vitro findings suggest that ketamine is a potent inhibitor of NF{kappa}B activation and cytokine production in rat PBMC.

Keywords: ketamine, nuclear factor-{kappa}B, tumor necrosis factor-{alpha}, mononuclear cells, endotoxemia




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