Kawasaki T, Ogata M, Kawasaki C, Ogata J, Inoue Y, Shigematsu A
Department of Anesthesiology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Anesth Analg. 1999 Sep;89(3):665-9. doi: 10.1097/00000539-199909000-00024.
The production of proinflammatory cytokines, such as tumor necrosis factor (TNF) a, interleukin (IL)-6, and IL-8, increases in patients with sepsis; marked production causes organ failure and septic shock. We previously reported that ketamine suppressed lipopolysaccharide (LPS)-induced TNF-alpha production in mice. However, there are no reports on the effect of ketamine on cytokine production in human whole blood. Therefore, in this study, we investigated the efficacy of ketamine on LPS-induced TNF-alpha, IL-6, and IL-8 production and recombinant human (rh) TNF-a-induced IL-6 and IL-8 production in human whole blood. After adding different doses of ketamine to whole blood, the blood was stimulated with LPS or rhTNF. After incubation, the plasma TNF-alpha activity and IL-6 and IL-8 concentrations were measured using the L929 cell cytotoxic assay or an enzyme-linked immunoassay. Ketamine significantly suppressed LPS-induced TNF-alpha production at concentrations >20 microg/mL. At concentrations >100 microg/mL, ketamine also significantly suppressed both LPS-induced and rhTNF-induced IL-6 and IL-8 production. In this study, we demonstrated that ketamine directly inhibits the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-8 in human whole blood.
We found that ketamine suppressed lipopolysaccharide-induced tumor necrosis factor alpha, interleukin (IL)-6, and IL-8 production and recombinant human tumor necrosis factor-induced IL-6 and IL-8 production in human whole blood. Ketamine directly suppresses proinflammatory cytokine production.
脓毒症患者体内促炎细胞因子如肿瘤坏死因子（TNF）α、白细胞介素（IL）-6和IL-8的产生会增加；大量产生会导致器官衰竭和感染性休克。我们之前报道过氯胺酮可抑制小鼠体内脂多糖（LPS）诱导的TNF-α产生。然而，尚无关于氯胺酮对人全血中细胞因子产生影响的报道。因此，在本研究中，我们调查了氯胺酮对人全血中LPS诱导的TNF-α、IL-6和IL-8产生以及重组人（rh）TNF-α诱导的IL-6和IL-8产生的作用。向全血中加入不同剂量的氯胺酮后，用LPS或rhTNF刺激血液。孵育后，使用L929细胞细胞毒性试验或酶联免疫吸附测定法测量血浆TNF-α活性以及IL-6和IL-8浓度。氯胺酮在浓度>20μg/mL时可显著抑制LPS诱导的TNF-α产生。在浓度>100μg/mL时，氯胺酮还可显著抑制LPS诱导的以及rhTNF诱导的IL-6和IL-8产生。在本研究中，我们证明氯胺酮可直接抑制人全血中TNF-α、IL-6和IL-8等促炎细胞因子的产生。
我们发现氯胺酮可抑制人全血中脂多糖诱导的肿瘤坏死因子α、白细胞介素（IL）-6和IL-8产生以及重组人肿瘤坏死因子诱导的IL-6和IL-8产生。氯胺酮可直接抑制促炎细胞因子的产生。
