Canadian Journal of Anesthesia

, Volume 47, Issue 10, pp 1019–1024 | Cite as

Ketamine suppresses endotoxin-induced NF-κB expression

  • Tetsuhiro Sakai
  • Takashi Ichiyama
  • Charles W. WhittenEmail author
  • Adolph H. Giesecke
  • James M. Lipton
Laboratory Investigations


Purpose: Ketamine reduces endotoxin-induced production of proinflammatory cytokines, including tumour necrosis factor- α (TNF), in several types of inflammatory cells, including monocytes and macrophages. Transcription of the genes that encode production of these proinflammatory cytokines is regulated by nuclear factor-kappa B (NF-κB). Cytoplasmic B protein is activated by endotoxin (LPS) as well as by TNF, allowing B protein to migrate into the cell nucleus to activate gene transcription for these inflammatory mediators. Because NF-κB is likely involved in brain injury and inflammatory neurodegenerative disease, such as multiple sclerosis, we examined whether ketamine inhibits LPS-induced activation of NF-κB in human glioma cellsin vitro and intact mouse brain cellsin vivo.

Methods: Endotoxin-induced NF-κB expression in both the human glioma cellsin vitro and the intact mouse brain cellsin vivo was determined by electrophoretic mobility shift assays (EMSA) of nuclear extracts and measurement of NF-κB expression by densitometry. Endotoxin was injected intracerebroventricularlyin vivo and intact brain was harvested. Klenow fragment labeling was used to identify NF-κB protein for both thein vivo andvitro experiments.

Results: Endotoxin treatment increased NF-κB expression (P<0.05) bothin vivo andvitro compared with control (untretaed) cells. Ketamine suppressed endotoxin-induced neuronal NF-κB activation in a dose-dependent manner (P<0.05, except for the 10−5M concentrationin vitro) bothin vivo andvitro.

Conclusion: Ketamine inhibits endotoxin-induced NF-κB expression in brain cellsin vivo andvitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators.


Ketamine Nuclear Extract Electrophoretic Mobility Shift Assay Human Glioma Cell Traumatic Spinal Cord Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Objectif: La kétamine réduit la production de cytokines pro-inflammatoires induite par endotoxine, y compris le facteur nécrosant des tumeurs (TNF), dans certains types de cellules inflammatoires comprenant les monocytes et les macrophages. La transcription des gènes qui encodent la production de ces cytokines pro-inflammatoires est réglée par le facteur-kappa B nucléaire (NF-6B). La protéine cytoplasmique 6B est activée par l’endotoxine (LPS) et par le TNF et peut ainsi migrer dans le noyau cellulaire et activer la transcription génique pour ces médiateurs de l’inflammation. Comme le NF-6B participe probablement aux lésions cérébrales et aux maladies inflammatoires neurodégénératives, dont la sclérose en plaques, notre but était de savoir si la kétamine inhibe l’activation de NF-6B induit par LPS dans des cellules de gliome humainin vitro et dans des cellules cérébrales intactes de sourisin vivo.

Méthode: L’expression du NF-6B induite par endotoxine dans les cellules humainesin vitro et dans les cellules de sourisin vivo a été déterminée par une étude de retardement de la mobilité électrophorétique (ERME) d’extraits nucléaires et la mesure de l’expression du NF-6B a été faite par densitométrie. L’endotoxine a été injectée dans les ventricules cérébrauxin vivo et du tissu cérébral intact a été prélevé. Le marquage de fragments de Klenow a été utilisé pour identifier la protéine du NF-6B des deux expériencesin vivo etvitro.

Résultats: Le traitement avec l’endotoxine a augmenté l’expression du NF-6B (P<0,05) des cellulesin vivo etin vitro comparées aux cellules témoin (non traitées). La kétamine a supprimé l’activation neuronale de NF-6B induite par endotoxine d’une façon dose-dépendante (P<0,05, sauf pour une concentration de 10−5Min vitro) des cellulesin vivo etin vitro.

Conclusion: La kétamine inhibe l’expression de NF-6B induite par endotoxine dans des cellules cérébralesin vivo etin vitro et on croit que cela pourrait contribuer aux effets neuroprotecteurs de la kétamine dont parlent d’autres chercheurs.


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Copyright information

© Canadian Anesthesiologists 2000

Authors and Affiliations

  • Tetsuhiro Sakai
    • 1
  • Takashi Ichiyama
    • 1
  • Charles W. Whitten
    • 1
    Email author
  • Adolph H. Giesecke
    • 1
  • James M. Lipton
    • 1
  1. 1.From the Departments of Anesthesiology and Pain Management and PhysiologyThe University of Texas Southwestern Medical Center at DallasDallasUSA

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