Takenaka I, Ogata M, Koga K, Matsumoto T, Shigematsu A
Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Anesthesiology. 1994 Feb;80(2):402-8. doi: 10.1097/00000542-199402000-00020.
The cytokines play important roles in the pathophysiologic alterations associated with sepsis, but there are no reports about the effect of anesthetics on their production. Therefore, the authors examined the effect of ketamine on lipopolysaccharide (LPS)-induced and calcium ionophore A23187-induced tumor necrosis factor alpha (TNF-alpha) production in thioglycolate (TGC)-elicited peritoneal macrophages (MPs) in ddY mice.
Ketamine was added to TGC-elicited MPs at various times after the stimulation with LPS or A23187. After the MPs were stimulated by LPS or A23187 and incubated, TNF-alpha activities in the supernatant of MPs were determined by an L929 cytotoxic assay. In vivo, the ddY mice were injected intraperitoneally with TGC. Four days later, they were injected subcutaneously with ketamine and then injected intravenously with LPS. Two hours after the LPS challenge, TNF-alpha activities of the sera were determined.
Ketamine suppressed both LPS-induced and A23187-induced TNF-alpha production in a dose-dependent manner. The simultaneous addition of ketamine to LPS-stimulated and A23187-stimulated MPs resulted in a 50% inhibition of TNF-alpha production at 20 micrograms/ml and 12.5 micrograms/ml, respectively. Ketamine also caused a significant suppression of TNF-alpha production even when added to the MPs 2 h after the LPS challenge. There was a significant decrease in A23187-induced TNF-alpha production in TGC-elicited MPs in a calcium-depleted medium when compared with that in a calcium-containing medium. Conversely, LPS-induced TNF-alpha production did not cause such a result. In addition, ketamine could suppress LPS-induced TNF-alpha production in TGC-pretreated mice in vivo.
Ketamine suppresses LPS-induced TNF-alpha production in both TGC-elicited MPs and TGC-pretreated mice.
细胞因子在脓毒症相关的病理生理改变中发挥重要作用，但关于麻醉药对其产生的影响尚无报道。因此，作者研究了氯胺酮对脂多糖（LPS）诱导的以及钙离子载体A23187诱导的肿瘤坏死因子α（TNF-α）在ddY小鼠巯基乙酸盐（TGC）诱导的腹腔巨噬细胞（MPs）中产生的影响。
在LPS或A23187刺激后的不同时间，将氯胺酮加入TGC诱导的MPs中。MPs经LPS或A23187刺激并孵育后，通过L929细胞毒性试验测定MPs上清液中的TNF-α活性。在体内，给ddY小鼠腹腔注射TGC。4天后，皮下注射氯胺酮，然后静脉注射LPS。LPS攻击2小时后，测定血清中的TNF-α活性。
氯胺酮以剂量依赖的方式抑制LPS诱导的和A23187诱导的TNF-α产生。在LPS刺激的和A23187刺激的MPs中同时加入氯胺酮，分别在20微克/毫升和12.5微克/毫升时导致TNF-α产生受到50%的抑制。即使在LPS攻击后2小时将氯胺酮加入MPs中，也能显著抑制TNF-α的产生。与含钙培养基相比，在缺钙培养基中，A23187诱导的TGC诱导的MPs中TNF-α产生显著降低。相反，LPS诱导的TNF-α产生未出现此结果。此外，氯胺酮可在体内抑制TGC预处理小鼠中LPS诱导的TNF-α产生。
氯胺酮在TGC诱导的MPs和TGC预处理的小鼠中均抑制LPS诱导的TNF-α产生。
