Larsen B, Hoff G, Wilhelm W, Buchinger H, Wanner G A, Bauer M
Department of Anesthesiology and Critical Care Medicine, University of the Saarland, Homburg/Saar, Germany.
Anesthesiology. 1998 Nov;89(5):1218-27. doi: 10.1097/00000542-199811000-00023.
Various anesthetics have been suggested to interfere with the immune system. The ability of leukocytes to express surface receptors and mediators is fundamental to a successful host defense. Therefore, the effects of intravenous anesthetics on cytokine release by leukocytes and expression of surface molecules known to modulate this response were determined.
Concentration-dependent effects of thiopentone, etomidate, propofol, ketamine, midazolam, and fentanyl on spontaneous and endotoxin (lipopolysaccharide; 1 microg/ml)-stimulated cytokine release were studied in whole blood from volunteers (n = 6) cultured for 25 h. In addition, expression of the lipopolysaccharide-recognition molecule CD14 and the major histocompatibility complex class II molecule human leukocyte locus A system-DR (HLA-DR) on monocytes were assessed using flow cytometry.
All anesthetics studied elicited only minor effects on spontaneous cytokine release even at pharmacologic concentrations. However, expression density of CD14 was reduced in the presence of thiopentone, etomidate, and propofol, whereas HLA-DR was unaffected. Lipopolysaccharide-stimulated tumor necrosis factor response was inhibited by thiopentone (12.8% [median]; 7.6-18.8 [25-75 percentile]) of control, and ketamine (46.4% [median]; 44.4-56.4 [25-75 percentile]), at pharmacologic concentrations, whereas it was augmented even in the presence of low concentrations of propofol (172.3% [median]; 120.5-200.7 [25-75 percentile]). Ketamine additionally decreased the concentration of interleukin (IL)-1beta (14.8% [median]; 12.0-18.0 [25-75 percentile]). Release of IL-1 receptor antagonist (IL-1ra) was inhibited by thiopentone, etomidate, and propofol, whereas the same anesthetics increased IL-10 concentration simultaneously. Midazolam and fentanyl did not alter the concentrations of any cytokine.
These results suggest a complex modulation of the cytokine response by the studied anesthetics in cultured whole blood. Although effects on spontaneous cytokine release by leukocytes were negligible, some anesthetics affected their ability to respond to lipopolysaccharide.
已有多种麻醉剂被认为会干扰免疫系统。白细胞表达表面受体和介质的能力是宿主成功防御的基础。因此，我们测定了静脉麻醉剂对白细胞释放细胞因子以及对已知可调节这种反应的表面分子表达的影响。
研究了硫喷妥钠、依托咪酯、丙泊酚、氯胺酮、咪达唑仑和芬太尼在浓度依赖情况下，对来自志愿者（n = 6）的全血自发释放细胞因子以及内毒素（脂多糖；1微克/毫升）刺激释放细胞因子的影响，全血培养25小时。此外，使用流式细胞术评估单核细胞上脂多糖识别分子CD14和主要组织相容性复合体II类分子人类白细胞位点A系统-DR（HLA-DR）的表达。
即使在药理浓度下，所有研究的麻醉剂对自发细胞因子释放仅产生轻微影响。然而，在硫喷妥钠、依托咪酯和丙泊酚存在的情况下，CD14的表达密度降低，而HLA-DR不受影响。在药理浓度下，硫喷妥钠（12.8%[中位数]；7.6 - 18.8[25 - 75百分位数]）和氯胺酮（46.4%[中位数]；44.4 - 56.4[25 - 75百分位数]）抑制了脂多糖刺激的肿瘤坏死因子反应，而即使在低浓度丙泊酚存在的情况下，该反应也增强（172.3%[中位数]；120.5 - 200.7[25 - 75百分位数]）。氯胺酮还降低了白细胞介素（IL）-1β的浓度（14.8%[中位数]；12.0 - 18.0[25 - 75百分位数]）。硫喷妥钠、依托咪酯和丙泊酚抑制了IL-1受体拮抗剂（IL-1ra）的释放，而相同的麻醉剂同时增加了IL-10的浓度。咪达唑仑和芬太尼未改变任何细胞因子的浓度。
这些结果表明，在培养的全血中，所研究的麻醉剂对细胞因子反应有复杂的调节作用。尽管对白细胞自发释放细胞因子的影响可忽略不计，但一些麻醉剂影响了它们对脂多糖的反应能力。
