异丙酚对脂多糖诱导人单核细胞释放细胞因子的影响

Effects of propofol on the cytokine release from human monocytes induced by lipopolysaccharide

目的观察异丙酚对脂多糖(LPS)诱导人单核细胞(THP1)释放细胞因子的影响。方法将体外培养的THP1细胞分为3组:对照组,1μg/mlLPS刺激组(L组),1μg/mlLPS+50μmol/L异丙酚组(L+P组)。采用LiquiChip液相蛋白芯片系统检测3组不同处理因素作用12h时对THP1细胞分泌粒细胞-巨噬细胞集落刺激因子(GM-CSF)、干扰素γ(IFN-γ)、白细胞介素1β(IL-1β)、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12、肿瘤坏死因子α(TNF-α)的影响。用不同浓度的异丙酚(0,12.5,25,50,100μmol/L)同1μg/mlLPS联合刺激THP1细胞(分别为B、C、D、E、F组),以未加任何刺激的THP1细胞为对照(A组),分析异丙酚对THP1细胞分泌IL-6、IL-8、TNF-α影响的剂量效应关系。结果与对照组相比,L组IL-1β、IL-6、IL-8和TNF-α均明显增高(P<0.01),而GM-CSF、IFN-γ、IL-2、IL-4、IL-10、IL-12的变化差异无统计学意义(P>0.05);与L组相比,L+P组THP1细胞释放IL-6、IL-8和TNF-α均明显降低(P<0.01)。与单独LPS刺激组(B组)比较,添加不同浓度异丙酚的各组(C、D、E、F组)IL-6、IL-8和TNF-α释放明显降低(P<0.05或0.01),且随着异丙酚剂量的增加,三者的释放呈递减趋势。结论LPS可诱导THP1细胞释放多种炎性细胞因子,异丙酚可呈剂量依赖性地抑制IL-6、IL-8和TNF-α的释放,这可能是其在内毒素血症的发生和发展中发挥保护作用的分子机制之一。

Objective To observe the effects of propofol on the cytokine release from human monocytic cell line （THP1） induced by lipopolysaccharide （LPS）. Methods THP1 cells cultured in vitro, and they were divided into 3 groups： 0 μg/ml LPS group, 1 μg/ml LPS group and 1μg/ml LPS＋50μmol/L propofol group, respectively, and incubated for 12 hours. Then the supernatant was collected from each culture for the determination of the levels of granulocyte/macrophage colony stimulating factor （GM-CSF）, interferon-γ （IFN-γ）, tumor necrosis factor-α （TNF-α） and interleukin （IL）-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and IL-12 by using LiquiChip system. Propol was added to the culture fluid of THP1 cells in the final concentrations of 0, 12.5, 25, 50 and 100μmol/L （for the groups B, C, D, E and F, respectively）, with 1μg/ml LPS. 12 hours later the supernatants were collected to detect the levels of IL-6, IL-8, TNF-α. Culture fluid without LPS and propofol （group A） was used as control. Results The levels of IL-1β, IL-6, IL-8 and TNF-α were elevated obviously in group L than that in control group （P〈0.01）, and no significant differences were found in levels of GM-CSF, IFN-γ, IL-2, IL-4, IL-10 and IL-12 compared between L and control groups （P〉0.05）. In group L＋P, levels of IL-6, IL-8 and TNF-α were significantly lower than that in group L （P〈0.05 or 0.01）. The levels of IL-6, IL-8 and TNF-α in groups C, D, E and F were lowered significantly compared with that in group B （P〈0.05 or 0.01）. With the increasing concentrations of propofol, IL-6 （F=129.61, P=0.00）, IL-8 （F=163.01, P=0.00） and TNF-α （F=259.96, P=0.00） were lowered gradually. Conclusion LPS may increase the release of IL-1β, IL-6, IL-8 and TNF-α from human monocytes. Propofol can dose-dependently inhibit the release of IL-6, IL-8 and TNF-α from monocytes stimulated by LPS.