Hecker Matthias, Linder Tomke, Ott Juliane, Walmrath Hans-Dieter, Lohmeyer Jürgen, Vadász István, Marsh Leigh M, Herold Susanne, Reichert Martin, Buchbinder Anja, Morty Rory Edward, Bausch Britta, Fischer Tobias, Schulz Richard, Grimminger Friedrich, Witzenrath Martin, Barnes Matt, Seeger Werner, Mayer Konstantin
University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany.
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Crit Care. 2015 May 12;19(1):226. doi: 10.1186/s13054-015-0933-6.
Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. As there is rising evidence about immuno-modulatory effects of lipid emulsions required for parenteral nutrition of ARDS patients, we sought to investigate whether infusion of conventional soybean oil (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty acids, respectively, may influence subsequent pulmonary inflammation.
In a randomized controlled, single-blinded pilot study, forty-two volunteers received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type and ChemR23 knockout mice were infused with both lipid emulsions and challenged with LPS intratracheally.
In volunteers receiving lipid emulsions, the fatty acid profile in the plasma and in isolated neutrophils and monocytes was significantly changed. Adhesion of isolated monocytes to endothelial cells was enhanced after infusion of SO and reduced by FO, however, no difference of infusion on an array of surface adhesion molecules was detected. In neutrophils and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in the SO and decreased in the FO group. LPS inhalation in volunteers evoked an increase in neutrophils in BAL fluids, which decreased faster in the FO group. While TNF-α in the BAL was increased in the SO group, IL-8 decreased faster in the FO group. In the murine model of lung injury, effects of FO similar to the volunteer group observed in wild-type mice were abrogated in ChemR23 knockout mice.
After infusion of conventional lipid emulsions, leukocytes exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines, and neutrophil recruitment into the alveolar space possibly mediated by ChemR23-signaling. Lipid emulsions thus exert differential effects in human volunteers and mice in vivo.
DRKS00006131 at the German Clinical Trial Registry, 2014/05/14.
急性呼吸窘迫综合征（ARDS）是重症监护病房患者死亡的主要原因。鉴于越来越多的证据表明，ARDS患者肠外营养所需的脂质乳剂具有免疫调节作用，我们试图研究分别输注富含n-6或n-3脂肪酸的传统大豆油（SO）基或鱼油（FO）基脂质乳剂是否会影响随后的肺部炎症。
在一项随机对照、单盲的试点研究中，42名志愿者接受了两天的SO、FO或生理盐水输注。此后，志愿者吸入预定义剂量的脂多糖（LPS），并在8或24小时后进行支气管肺泡灌洗（BAL）。在LPS诱导的肺损伤小鼠模型中，研究了消退素E1（RvE1）受体ChemR23的可能参与情况。野生型和ChemR23基因敲除小鼠均经气管内输注两种脂质乳剂并接受LPS刺激。
在接受脂质乳剂输注的志愿者中，血浆以及分离出的中性粒细胞和单核细胞中的脂肪酸谱发生了显著变化。输注SO后，分离出的单核细胞与内皮细胞的黏附增强，而FO则使其降低，然而，未检测到输注对一系列表面黏附分子有差异。在中性粒细胞和单核细胞中，SO组中LPS诱导的促炎细胞因子生成增加，而FO组中则减少。志愿者吸入LPS后，BAL液中的中性粒细胞增多，而FO组中中性粒细胞减少得更快。SO组BAL中的TNF-α增加，而FO组中IL-8减少得更快。在肺损伤小鼠模型中，在野生型小鼠中观察到的与志愿者组相似的FO效应在ChemR23基因敲除小鼠中消失。
输注传统脂质乳剂后，白细胞表现出增强的黏附性和促炎特性。相比之下，基于FO的脂质乳剂可降低单核细胞黏附、减少促炎细胞因子生成，并可能通过ChemR23信号传导减少中性粒细胞向肺泡腔的募集。脂质乳剂在人类志愿者和小鼠体内发挥不同的作用。
德国临床试验注册中心，注册号DRKS00006131，2014年5月14日。
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