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

Purpose: To investigate the efficacy of S(+)-ketamine and R(-)-ketamine on staphylococcal enterotoxin B (SEB)-induced tumour necrosis factor (TNF)-, i nterleukin (IL)-6, and IL-8 production in human whole blood in vitro. Methods: After Ethics Committee approval and informed consent, blood sample s were obtained from ten healthy volunteers and diluted with five volumes o f RPMI 1640. After adding different doses of ketamine isomers (0-1000 muM), the blood was stimulated with SEB (10 ng.mL(-1)). After a six-hour incubat ion period, the plasma TNF- activity was determined by the L929 cell cytoto xic assay and IL-6 and IL-8 concentrations were measured using an enzyme-li nked immunoassay. Results: Ketamine isomers significantly suppressed SEB-induced TNF- product ion at concentrations exceeding 50 muM. Ketamine isomers at concentrations exceeding 100 muM also significantly suppressed SEB-induced IL-6 production . Furthermore, ketamine isomers at concentrations exceeding 500 muM signifi cantly suppressed SEB-induced IL-8 production. There were no significant di fferences between the suppressive effects of S(+)-ketamine and R(-)-ketamin e on SEB-induced proinflammatory cytokine production. Conclusion: This study demonstrated that ketamine isomers suppressed SEB-in duced TNF-, IL-6, and IL-8 production in human whole blood.