Effect of linezolid on cytokine production capacity and plasma endotoxin levels in response to lipopolysaccharide stimulation of whole blood
Effect of linezolid on cytokine production capacity and plasma endotoxin levels in response to lipopolysaccharide stimulation of whole blood
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DOI：
10.1007/s10156-009-0012-5
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发表时间：
2010-04-01
影响因子：
2.2
通讯作者：
Endo, Shigeatsu
中科院分区：
文献类型：
--
作者：
Takahashi, Gaku;Sato, Nobuhiro;Endo, Shigeatsu
本研究的目的是评估利奈唑胺（LZD）存在下脂多糖（LPS）刺激的细胞因子产生，并与药物对血浆内毒素水平的影响进行比较。用10 μ g/ml LPS刺激从5名健康受试者收集的外周静脉全血样品。然后将LZD以0、2、4和15 μ g/ml的浓度加入到LPS刺激的血液样品中，然后在37 ℃、5%CO2 -95%空气气氛中孵育24小时。测定所得培养物的上清液以确定肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ、白细胞介素（IL）-10、单核细胞趋化蛋白（MCP）-1和内毒素的水平。与0 μ g/ml组相比，在LZD 2、4和15 μ g/ml组中观察到TNF-α和IFN-γ水平的显著降低（Dunnett程序; P < 0.05）。IL-10水平倾向于增加，与LZD浓度无关;然而，未观察到显著的组间差异[方差分析（ANOVA）; P = 0.68]。与0 μ g/ml组相比，在LZD 2、4或15 μ g/ml组中未观察到内毒素水平的显著降低，组间差异无显著性（ANOVA; P = 0.83）。无论LZD浓度如何，均未观察到MCP-1水平的变化（ANOVA; P = 0.82）。总结：（1）LZD可能在有限程度上抑制INF-γ和TNF-α的产生;（2）LZD对细菌产生内毒素没有任何抑制作用，但抑制细胞因子的产生。结果表明，LZD可能在挽救脓毒症患者的生命方面具有重要作用。
The purpose of this study was to assess lipopolysaccharide (LPS)-stimulated cytokine production in the presence of linezolid (LZD) in comparison with the drug effect on the plasma endotoxin level. Peripheral venous whole-blood samples collected from five healthy subjects were stimulated with 10 mu g/ml of LPS. LZD was then added to the LPS-stimulated blood samples at concentrations of 0, 2, 4, and 15 mu g/ml, followed by incubation for 24 h at 37A degrees C in a 5% CO2-95% air atmosphere. Supernatants of the resultant cultures were assayed to determine the levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, and endotoxin. Significant decreases in the levels of TNF-alpha and IFN-gamma were observed in the LZD 2, 4, and 15 mu g/ml groups as compared with that in the 0 mu g/ml group (Dunnett's procedure; P < 0.05). The level of IL-10 tended to increase irrespective of the LZD concentration; however, no significant intergroup differences were observed [analysis of variance (ANOVA); P = 0.68]. No significant decrease of the endotoxin level was observed in the LZD 2, 4, or 15 mu g/ml groups as compared with that in the 0 mu g/ml group, with no significant intergroup differences (ANOVA; P = 0.83). No change in the MCP-1 levels was observed irrespective of the LZD concentration (ANOVA; P = 0.82). To conclude: (1) it appears possible that LZD inhibits the production of INF-gamma and TNF-alpha to a limited extent; (2) LZD did not exert any inhibitory effect on endotoxin production by bacteria, while suppressing cytokine production. The results indicate that LZD may have a significant role in saving the lives of patients with sepsis.