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Ketamine isomers suppress superantigen-induced proinflammatory cytokine production in human whole blood

[Les isomères de la kétamine suppriment la production de cytokine pro-inflammatoire induite par des superantigènes dans le sang complet humain]

From the Department of Anesthesiology, University of Occupational and Environmental Health, Kitakyushu, Japan.

Address correspondence to: Dr. Masanori Ogata, Department of Anesthesiology, University of Occupational and Environmental Health, 1-1-1 Iseigaoka Yahatanishiku Kitakyushu, 807-8555, Japan. Phone: +81-93-691-7265; Fax: +81-93-601-2910; E-mail: mogata{at}med.uoeh-u.ac.jp

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 blood in 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.

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