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

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.