Ketamine Reduces NFκB Activation and TNFα Production in Rat Mononuclear Cells Induced by Lipopolysaccharide In Vitro

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 TNFα and IL-6. NFκB 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 NFκB activation and TNFα 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 NFκB was determined by electrophoretic mobility shift assay (EMSA), and the expression of IκBα, its inhibitor, in PBMC was analysed by Western blotting. TNFα levels in the supernatants were measured using a specific enzyme-linked immunosorbent assay (ELISA). LPS stimulation of rat PBMC increased TNFα production and NFκB activation, with corresponding loss of IκBα. Ketamine significantly reduced the LPS-induced NFκB activation and inhibited TNFα production in a dose-dependent manner. These in vitro findings suggest that ketamine is a potent inhibitor of NFκB activation and cytokine production in rat PBMC. (received 8 November 2002, accepted 8 February 2002)