Xenon and isoflurane differentially modulate lipopolysaccharide-induced activation of the nuclear transcription factor KB and production of tumor necrosis factor-α and interleukin-6 in monocytes
Xenon and isoflurane differentially modulate lipopolysaccharide-induced activation of the nuclear transcription factor KB and production of tumor necrosis factor-α and interleukin-6 in monocytes
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DOI：
10.1213/01.ane.0000106860.27791.44
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发表时间：
2004-04-01
影响因子：
5.7
通讯作者：
Rossaint, R
中科院分区：
文献类型：
--
作者：
de Rossi, LW;Brueckmann, M;Rossaint, R
已知麻醉剂会干扰炎性细胞因子的产生。在这项研究中，我们研究了氙和异氟烷对脂多糖（LPS）诱导的核转录因子（NF）-kappaB活化以及肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的体外产生的影响。在不存在或存在氙（30和60 μ g/ml）和异氟烷（1和2最小肺泡麻醉浓度[MAC]）的情况下，将全血与LPS孵育。4小时后，在上清液中测定TNF-α和IL-6。使用从血液样品分离的单核细胞研究NF-κ B的参与。制备全细胞裂解物，并使用基于酶联免疫吸附测定的NF-κ B试剂盒测量NF-κ B p50和p65亚基与其靶DNA的结合。与对照组相比，氙存在时LPS诱导的TNF-α和IL-6的产生以及NF-κ B的活化显著增加。相反，异氟烷抑制NF-κ B的活化，这与TNF-α和IL-6的产生减少有关。我们的研究结果表明，氙和异氟烷对LPS诱导的TNF-α和IL-6的产生具有相反的作用。此外，氙增加，而异氟烷抑制NF-κ B的活化，提供了一个可能的分子机制，对单核细胞TNF-α和IL-6的产生的不同影响。
Anesthetics are known to interfere with the production of inflammatory cytokines. In this study, we investigated the effect of xenon and isoflurane on the lipopolysaccharide (LPS)-induced activation of the nuclear transcription factor (NF)-kappaB and production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in vitro. Whole blood was incubated with LPS in the absence or presence of the either xenon (30 and 60 Vol%) and isoflurane (1 and 2 minimum alveolar anesthetic concentration [MAC]). After 4 h, TNF-alpha and IL-6 were assayed in the supernatant. Involvement of NF-kappaB was investigated using isolated monocytes from the blood samples. Whole-cell lysates were prepared, and binding of the NF-kappaB p50 and p65 subunit to its target DNA were measured with an enzyme-linked immunosorbent assay-based NF-kappaB kit. LPS-induced production of TNF-alpha and IL-6 as well as activation of NF-kappaB were significantly increased in the presence of xenon compared with controls. In contrast, isoflurane inhibited the activation of NF-kappaB, which was associated with a decreased production of TNF-alpha and IL-6. Our results demonstrate that xenon and isoflurane have opposite effects on the LPS-induced production of TNF-alpha and IL-6. Furthermore, xenon increases, whereas isoflurane inhibits the activation of NF-kappaB, providing a possible molecular mechanism for the different effects on monocyte TNF-alpha and IL-6 production.