Giraud O, Seince P F, Rolland C, Leçon-Malas V, Desmonts J M, Aubier M, Dehoux M
Unité INSERM 408, Faculté de Médecine Xavier Bichat, Paris, France.
Am J Respir Crit Care Med. 2000 Dec;162(6):2278-86. doi: 10.1164/ajrccm.162.6.9807113.
Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific effect of halothane on this response.
多项研究表明，麻醉剂可调节免疫反应。本研究旨在探讨氟烷和硫喷妥钠对肺部炎症反应的影响。将接受或未接受气管内（IT）注入脂多糖（LPS）的大鼠分别用氟烷（0.5%、1%或1.5%）或硫喷妥钠（60 mg·kg⁻¹）麻醉，并进行机械通气4小时。对照大鼠在未麻醉的情况下接受或不接受LPS处理。通过支气管肺泡灌洗液（BALF）中的总细胞计数和分类细胞计数以及BALF和肺匀浆中的细胞因子测量（肿瘤坏死因子-α [TNF-α]、白细胞介素-6 [IL-6]、巨噬细胞炎性蛋白-2 [MIP-2]和单核细胞趋化蛋白-1 [MCP-1]）来评估肺部炎症。在未进行LPS处理时，氟烷和硫喷妥钠均未改变气管切开术或机械通气所诱导的中度炎症反应。在所有接受IT LPS的组中，细胞募集和细胞因子浓度均升高。然而，在氟烷麻醉的大鼠（氟烷≥1%）中，而非硫喷妥钠麻醉的大鼠中，LPS诱导的肺部炎症以剂量依赖的方式发生改变。实际上，使用1%氟烷时，多形核白细胞（PMN）募集减少了55%（p < 0.001），BALF和肺匀浆中的TNF-α、IL-6和MIP-2浓度降低了60%以上（p < 0.001），而总蛋白和MCP-1浓度保持不变。MIP-2的降低（在蛋白质和信使核糖核酸 [mRNA]水平均观察到）与PMN募集的减少密切相关（r = 0.73，p < 0.05）。这种氟烷减轻的肺部炎症反应是短暂的，在麻醉结束后20小时恢复。我们的研究表明，通过机械通气持续4小时给予的氟烷≥1%，而非机械通气本身，会改变大鼠早期LPS诱导的肺部炎症，提示氟烷对该反应具有特定作用。
