Inhibition of intracellular tumour necrosis factor (TNF)-α and interleukin (IL)-6 production in human monocytes by iloprost
Inhibition of intracellular tumour necrosis factor (TNF)-α and interleukin (IL)-6 production in human monocytes by iloprost
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DOI：
10.1046/j.1365-2362.2003.01241.x
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发表时间：
2003-11-01
影响因子：
5.5
通讯作者：
Sablotzki, A
中科院分区：
文献类型：
--
作者：
Czeslick, EG;Simm, A;Sablotzki, A
背景 为了研究伊洛前列素作为稳定的前列环素类似物对通过流式细胞术评估的全血系统中脂多糖 (LPS) 刺激的人单核细胞的 IL-6 和 TNF-α 的细胞内表达的影响。 材料和方法 六名健康志愿者的全血在停药后立即处理并在不同的日子进行两次（每个实验六次测量）在两种不同的环境中用 LPS 刺激（最终浓度 0.2 ng mL(-1) 和 10 ng mL(-1)) 与伊洛前列素（每个实验的终浓度分别为 0.01 nm、0.1 nm、0.3 nm、1 nm、3 nm、10 nm、30 nm 和 100 nm）在 37 ℃、5% CO2 下孵育 3 h。通过流式细胞术评估细胞内IL-6和TNF-α的表达。结果我们的研究首次表明，伊洛前列素（0.1 nm至100 nm）对LPS（10 ng mL（-1））刺激的人单核细胞产生IL-6产生剂量依赖性抑制作用，在低浓度LPS（0.2 ng mL（-1））刺激的单核细胞中更为明显。发现伊洛前列素（0.1 nm 至 100 nm）以剂量依赖性方式抑制 LPS 刺激的单核细胞产生 TNF-α，且不受 LPS 浓度的影响。 结论 除了血管舒张和抗血栓作用外，伊洛前列素还可能下调人单核细胞中 IL-6 和 TNF-α 的细胞内表达。
Background To investigate the effects of iloprost as a stable prostacyclin analogue on intracellular expression of IL-6 and TNF-alpha of lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system assessed by flow cytometry.Material and methods Whole blood of six healthy volunteers processed immediately after withdrawal and twice on different days (six measurements per experiment) was stimulated in two different settings with LPS (final concentrations 0.2 ng mL(-1) and 10 ng mL(-1)) and incubated with iloprost (final concentrations in each experiment were 0.01 nm, 0.1 nm, 0.3 nm, 1 nm, 3 nm, 10 nm, 30 nm and 100 nm) for 3 h at 37 degreesC and 5% CO2. Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry.Results Our investigations showed, for the first time, that iloprost (0.1 nm up to 100 nm) caused a dose-dependent inhibitory effect of IL-6 production in human monocytes stimulated with LPS (10 ng mL(-1)), which was even more obvious in monocytes stimulated with lower concentrated LPS (0.2 ng mL(-1)). Iloprost (0.1 nm up to 100 nm) was found to inhibit TNF-alpha production of LPS-stimulated monocytes in a dose-dependent fashion not influenced by LPS concentration.Conclusions Apart from the vasodilatory and antithrombotic effects, iloprost may also down-regulate the intracellular expression of IL-6 and TNF-alpha in human monocytes.