Galley H F, Dubbels A M, Webster N R
Academic Unit of Anaesthesia and Intensive Care, University of Aberdeen, Scotland.
Anesth Analg. 1998 Jun;86(6):1289-93. doi: 10.1097/00000539-199806000-00030.
Anesthetics and sedatives contribute to postoperative immunosuppression. Interleukin-8 (IL-8) is a chemotactic and activating factor that mediates neutrophil adhesion and margination and is essential for host defense. We investigated the effect of anesthetics on isolated human polymorphonuclear leukocyte production of IL-8. Healthy human polymorphonuclear leukocytes were isolated using a single-step density gradient and stimulated with lipopolysaccharide in the presence of varying concentrations of propofol or midazolam for up to 20 h. IL-8 was measured in both culture supernatants and cell lysates using enzyme immunoassay, and IL-8 mRNA in cells was measured using Northern blotting and phosphorimaging. Data were analyzed using Kruskal-Wallis analysis of variance or the Mann-Whitney U-test as appropriate. Lipopolysaccharide increased extracellular accumulation of interleukin-8, which was suppressed by both propofol (P = 0.025) and midazolam (P = 0.028). However, intracellular IL-8 increased with exposure to lipopolysaccharide (P = 0.028) and remained increased with both anesthetics. Northern blot analysis also revealed increased IL-8 mRNA levels in the presence of both midazolam and propofol, which was confirmed by molecular imaging. These data strongly suggest that the anesthetics modulate transport or secretion of IL-8 protein from the cell. Suppression of IL-8 by anesthetics and sedatives may predispose postoperative and intensive care patients to infection.
Anesthesia causes immune suppression and alters neutrophil function. We investigated the effect of propofol and midazolam on interleukin-8, a neutrophil chemotactic agent in human neutrophils. Both anesthetics decreased extracellular interleukin-8 accumulation, but intracellular levels and mRNA remained high. This suggests that propofol and midazolam alter interleukin-8 secretion from cells.
麻醉剂和镇静剂会导致术后免疫抑制。白细胞介素-8（IL-8）是一种趋化和激活因子，介导中性粒细胞黏附和边缘化，对宿主防御至关重要。我们研究了麻醉剂对分离的人多形核白细胞产生IL-8的影响。使用单步密度梯度分离健康人多形核白细胞，并在不同浓度的丙泊酚或咪达唑仑存在下用脂多糖刺激长达20小时。使用酶免疫测定法测量培养上清液和细胞裂解物中的IL-8，并使用Northern印迹和荧光成像测量细胞中的IL-8 mRNA。根据情况使用Kruskal-Wallis方差分析或Mann-Whitney U检验分析数据。脂多糖增加了白细胞介素-8的细胞外积累，丙泊酚（P = 0.025）和咪达唑仑（P = 0.028）均对其有抑制作用。然而，细胞内IL-8随着脂多糖暴露而增加（P = 0.028），并且在两种麻醉剂作用下均保持增加。Northern印迹分析还显示，在咪达唑仑和丙泊酚存在下，IL-8 mRNA水平增加，这通过分子成像得到证实。这些数据强烈表明，麻醉剂调节IL-8蛋白从细胞中的转运或分泌。麻醉剂和镇静剂对IL-8的抑制作用可能使术后和重症监护患者易发生感染。
麻醉会导致免疫抑制并改变中性粒细胞功能。我们研究了丙泊酚和咪达唑仑对人中性粒细胞中中性粒细胞趋化剂白细胞介素-8的影响。两种麻醉剂均降低了细胞外白细胞介素-8的积累，但细胞内水平和mRNA仍然很高。这表明丙泊酚和咪达唑仑改变了细胞中白细胞介素-8的分泌。
