de Rossi Lothar W, Brueckmann Martina, Rex Steffen, Barderschneider Marco, Buhre Wolfgang, Rossaint Rolf
*Department of Anesthesiology, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen; and †Department of Cardiology, University Hospital, Mannheim, Germany.
Anesth Analg. 2004 Apr;98(4):1007-1012. doi: 10.1213/01.ANE.0000106860.27791.44.
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.
This study has shown that monocytes respond to lipopolysaccharide (LPS) in the presence of xenon with an increased activation of nuclear transcription factor (NF)-kappaB, whereas isoflurane inhibits LPS-induced activation of NF-kappaB. These findings suggest a possible molecular mechanism for the different effects of both anesthetics on monocyte tumor necrosis factor-alpha and interleukin-6 production.
已知麻醉剂会干扰炎性细胞因子的产生。在本研究中，我们在体外研究了氙气和异氟烷对脂多糖（LPS）诱导的核转录因子（NF）-κB激活以及肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6产生的影响。全血在不存在或存在氙气（30%和60%体积分数）及异氟烷（1和2最低肺泡有效浓度[MAC]）的情况下与LPS一起孵育。4小时后，检测上清液中的TNF-α和IL-6。使用从血样中分离的单核细胞研究NF-κB的参与情况。制备全细胞裂解物，并用基于酶联免疫吸附测定的NF-κB试剂盒测量NF-κB p50和p65亚基与其靶DNA的结合。与对照组相比，在存在氙气的情况下，LPS诱导的TNF-α和IL-6产生以及NF-κB激活显著增加。相比之下，异氟烷抑制NF-κB的激活，这与TNF-α和IL-6产生减少有关。我们的结果表明，氙气和异氟烷对LPS诱导的TNF-α和IL-6产生具有相反的作用。此外，氙气增加而异氟烷抑制NF-κB的激活，这为对单核细胞TNF-α和IL-6产生的不同影响提供了一种可能的分子机制。
本研究表明，单核细胞在存在氙气的情况下对脂多糖（LPS）的反应是核转录因子（NF）-κB激活增加，而异氟烷抑制LPS诱导的NF-κB激活。这些发现为两种麻醉剂对单核细胞肿瘤坏死因子-α和白细胞介素-6产生的不同影响提供了一种可能的分子机制。
