Abstract
Purpose
To investigate the efficacy of S(+)-ketamine and R(−)-ketamine on staphylococcal enterotoxin B (SEB)-induced tumour necrosis factor (TNF)-, interleukin (IL)-6, and IL-8 production in human whole bloodin vitro.
Methods
After Ethics Committee approval and informed consent, blood samples were obtained from ten healthy volunteers and diluted with five volumes of RPMI 1640. After adding different doses of ketamine isomers (0–1000 μM), the blood was stimulated with SEB (10 ng·mL−1). After a six-hour incubation period, the plasma TNF-activity was determined by the L929 cell cytotoxic assay and IL-6 and IL-8 concentrations were measured using an enzyme-linked immunoassay.
Results
Ketamine isomers significantly suppressed SEB-induced TNF-production at concentrations exceeding 50 μM. Ketamine isomers at concentrations exceeding 100 μM also significantly suppressed SEB-induced IL-6 production. Furthermore, ketamine isomers at concentrations exceeding 500 μM significantly suppressed SEB-induced IL-8 production. There were no significant differences between the suppressive effects of S(+)-ketamine and R(−)-ketamine on SEB-induced proinflammatory cytokine production.
Conclusion
This study demonstrated that ketamine isomers suppressed SEB-induced TNF-, IL-6, and IL-8 production in human whole blood.
Résumé
Objectif
Vérifier l’efficacité de la S(+)-kétamine et de la R(−)-kétamine sur la production du facteur nécrosant des tumeurs (FNT)-a, de l’interleukine (IL)-6 et de l’IL-8, induits par l’entérotoxine B d’origine staphylococcique (EBS), dans le sang complet humain in vitro.
Méthode
Après avoir obtenu l’approbation du Comité d’éthique et le consentement éclairé des participants, nous avons recueilli des échantillons sanguins chez dix volontaires en santé et les avons dilué dans cinq volumes de RPMI 1640. Après l’addition de différentes doses d’isomères de kétamine (0–1000 μM), le sang a été stimulé avec l’EBS (10 ng·mL−1). À la suite d’une incubation de six heures, l’activité plasmatique de TNF-a a été déterminée par le dosage de la cytotoxicité cellulaire L929, et les concentrations d’IL-6 et d’IL-8 ont été mesurées au moyen d’un dosage immuno-enzymatique.
Résultats
Les isomères de kétamine ont supprimé de façon significative la production du TNF-a induit par l’EBS à des concentrations dépassant 50 μM, la production d’IL-6 induite par l’EBS à des concentrations au delà de 100 μM et la production d’IL-8 induite par l’EBS à des concentrations de plus de 500 μM. Il n’y a pas eu de différence significative entre les effets suppresseurs de la S(+)-kétamine et de la R(−)-kétamine sur la production de cytokine pro-inflammatoire induite pas l’EBS.
Conclusion
Cette étude démontre que les isomères de kétamine suppriment la production du FNT-a, d’IL-6 et d’IL-8, induits par l’EBS, dans le sang complet humain.
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This work was supported, in part, by Grant-in-Aid for Scientific Research 10671453, 12770850 from the Ministry of Education, Science, Sport, and Culture of Japan.
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Kawasaki, C., Kawasaki, T., Ogata, M. et al. Ketamine isomers suppress superantigen-induced proinflammatory cytokine production in human whole blood. Can J Anesth 48, 819–823 (2001). https://doi.org/10.1007/BF03016701
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DOI: https://doi.org/10.1007/BF03016701