Czeslick E G, Simm A, Grond S, Silber R-E, Sablotzki A
Department of Anaesthesiology and Critical Care Medicine, Martin Luther University Halle, Halle, Germany.
Eur J Clin Invest. 2003 Nov;33(11):1013-7. doi: 10.1046/j.1365-2362.2003.01241.x.
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.
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 degrees C and 5% CO2. Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry.
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.
Apart from the vasodilatory and antithrombotic effects, iloprost may also down-regulate the intracellular expression of IL-6 and TNF-alpha in human monocytes.
通过流式细胞术评估在全血系统中,伊洛前列素作为一种稳定的前列环素类似物对脂多糖(LPS)刺激的人单核细胞中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)细胞内表达的影响。
六名健康志愿者的全血在采集后立即进行处理,并在不同日期处理两次(每次实验六次测量),在两种不同条件下用LPS(终浓度分别为0.2 ng/mL和10 ng/mL)刺激,然后与伊洛前列素(每个实验中的终浓度分别为0.01 nM、0.1 nM、0.3 nM、1 nM、3 nM、10 nM、30 nM和100 nM)在37℃、5%二氧化碳条件下孵育3小时。通过流式细胞术评估IL-6和TNF-α的细胞内表达。
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)刺激的人单核细胞中IL-6的产生具有剂量依赖性抑制作用,在低浓度LPS(0.2 ng/mL)刺激的单核细胞中这种作用更明显。发现伊洛前列素(0.1 nM至100 nM)以剂量依赖性方式抑制LPS刺激的单核细胞中TNF-α的产生,且不受LPS浓度影响。
除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。