Ketamine reduces NFkappaB activation and TNFalpha 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 TNFalpha and IL-6. NFkappaB 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 NFkappaB activation and TNFalpha 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 NFkappaB was determined by electrophoretic mobility shift assay (EMSA), and the expression of IkappaBalpha, its inhibitor, in PBMC was analysed by Western blotting. TNFalpha levels in the supernatants were measured using a specific enzyme-linked immunosorbent assay (ELISA). LPS stimulation of rat PBMC increased TNFalpha production and NFkappaB activation, with corresponding loss of IkappaBalpha. Ketamine significantly reduced the LPS-induced NFkappaB activation and inhibited TNFalpha production in a dose-dependent manner. These in vitro findings suggest that ketamine is a potent inhibitor of NFkappaB activation and cytokine production in rat PBMC.
Yu
Yingqun
Y
Department of Anesthesiology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu, PR China.
Zhou
Zhiqiang
Z
Xu
Jianguo
J
Liu
Zhihai
Z
Wang
Yu
Y
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine