The Immunomodulatory Effect of Sevoflurane in Endotoxin-Injured Alveolar Epithelial Cells
BACKGROUND: Endotoxin-induced lung injury is a useful experimental system for the
characterization of immunopathologic mechanisms in acute lung injury. Although
alveolar epithelial cells (AEC) are directly exposed to volatile anesthetics, there is
limited information about the effect of anesthetics on these cells. In this study we
investigated the effect of pretreatment with the inhaled anesthetic sevoflurane on
lipopolysaccharide (LPS)-injured AEC.
METHODS: AEC were incubated with 1.1 vol % sevoflurane for 0.5 h, followed by LPS
stimulation for 5 h. Expression of monocyte chemoattractant protein-1 (MCP-1),
macrophage inflammatory protein-1 (MIP-1), macrophage inflammatory protein-2
(MIP-2), cytokine-induced neutrophil chemoattractant-1 (CINC-1), and intercellular
adhesion molecule-1 (ICAM-1) was analyzed. In addition, functional tests were
performed through chemotaxis and adherence assays to underline the biological
relevance of the findings.
RESULTS: Exposure of AEC to sevoflurane resulted in a 50% downregulation of
MCP-1 protein in the sevoflurane-LPS group when compared with non-sevoflurane-
LPS cells (P 0.05). MIP-1 concentration in LPS-stimulated cells decreased by
32% with sevoflurane (P 0.05), MIP-2 by 29% (P 0.05), and CINC-1 by 20% (P
0.05). ICAM-1 protein expression was attenuated by 36% (P 0.05). This inhibition
caused substantial changes in the inflammatory response of neutrophils. 33% less
chemotactic activity was seen in sevoflurane-treated LPS cells (P 0.001) as well as
47% decreased adhesion of neutrophils to AEC (P 0.001).
CONCLUSIONS: This study shows that sevoflurane alters the LPS-induced inflammatory
response, not only with respect to the expression pattern of inflammatory
mediators, but also regarding the biological consequences with less accumulation
of effector cells such as neutrophils
七氟烷对内毒素引起的肺泡上皮细胞损伤的免疫调节效应
背景:内毒素引起的肺损伤是用于描述急性肺损伤免疫病理学机制的一项有用的实验系统。尽管肺泡上皮细胞直接暴露于吸入麻醉药中,但关于麻醉药对这些细胞影响的研究信息尚少。在本研究中我们探讨了使用吸入麻醉药七氟烷预处理对内毒素引起的肺泡上皮细胞损伤的影。
方法:首先使用1.1%的七氟烷培育肺泡上皮细胞0.5h,接着使用脂多糖刺激5h。检测单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1β(MIP-1β)、巨噬细胞炎性蛋白-2(MIP-2)、中性粒细胞趋化因子-1(CINC-1)、细胞间黏附分子-1(ICAM-1)的表达水平。通过测定趋化性及黏附分析进行功能试验以确定发现的生物学相关性。
结果:与非七氟烷-脂多糖暴露组细胞相比,七氟烷暴露可使MCP-1表达下调50%(P<0.05),使用七氟烷可使LPS刺激细胞产生MIP-1β的浓度下降32%(P<0.05)、MIP-2下降29%(P<0.05),CINC-1下降20%(P<0.05),ICAM-1的表达下降36%(P<0.05)。这些抑制效应使得由中性粒细胞产生的炎症反应产生了重要的改变。七氟烷处理组的LPS刺激细胞的趋化性下降了33%(p<0.01),同时中性粒细胞黏附到肺泡上皮细胞的能力下降了47%(p<0.01)。
结论:本研究发现七氟烷可改变LPS引起的炎症反应,不仅仅是表现为炎症因子的表达改变,并且还可引起相应的生物学改变,表现为效应细胞的集聚减少,比如中性粒细胞。 |