Urbaschek R, McCuskey R S, Rudi V, Becker K P, Stickel F, Urbaschek B, Seitz H K
Institute for Medical Microbiology and Hygiene, Klinikum Mannheim, University of Heidelberg, Germany.
Alcohol Clin Exp Res. 2001 Feb;25(2):261-8.
Chronic alcohol ingestion leads to endotoxemia which is believed to play an important role in the pathogenesis of alcoholic liver disease (ALD). The purpose of this study was to determine if chronic ethanol consumption, in addition to affecting plasma endotoxin and cytokines, also affects the endotoxin-neutralizing capacity (ENC), sCD14, and sICAM-1, in patients with ALD. A second aim was to identify correlations between these latter parameters, endotoxin, and cytokines, especially IL-10.
Hospitalized patients with various degrees of ALD (n = 59), and 20 healthy volunteers were studied. Plasma endotoxin and ENC were determined using our kinetic Limulus amebocyte lysate test. Cytokines, sCD14, and sICAM-1 were measured by enzyme-linked immunosorbent assay.
Patients with ALD exhibited a mild endotoxemia (p < 0.01) and a marked decrease in ENC (p < 0.0002). TNF-alpha (p < 0.05), IL-6 (p < 0.0001), sICAM (p < 0.005), and sCD14 (p < 0.0005) were significantly elevated in all patients with ALD, and IL-10 (p < 0.05) in patients with cirrhotic ALD. With the exception of IL-10, the cytokines correlated with each other and with sICAM-1. No correlations occurred between endotoxin, ENC, and sCD14, and between these and the cytokines and sICAM-1. Elevated levels of endotoxin correlate with acute excessive alcohol ingestion. No gender differences were observed.
Acute alcohol intoxication rather than severe ALD results in significant endotoxemia. The limited capacity of plasma to neutralize endotoxin in liver injury seems to be an important factor in ALD which may be responsible for the release of endotoxin-induced mediators, such as cytokines, as well as s-ICAM-1, that are relevant in the pathogenesis of ALD.
长期摄入酒精会导致内毒素血症，这被认为在酒精性肝病（ALD）的发病机制中起重要作用。本研究的目的是确定慢性乙醇摄入除了影响血浆内毒素和细胞因子外，是否还会影响ALD患者的内毒素中和能力（ENC）、可溶性CD14（sCD14）和可溶性细胞间黏附分子-1（sICAM-1）。第二个目的是确定这些参数与内毒素、细胞因子尤其是白细胞介素-10（IL-10）之间的相关性。
对59例不同程度ALD的住院患者和20名健康志愿者进行研究。采用我们的动态鲎试剂法测定血浆内毒素和ENC。通过酶联免疫吸附测定法检测细胞因子、sCD14和sICAM-1。
ALD患者表现出轻度内毒素血症（p < 0.01）和ENC显著降低（p < 0.0002）。所有ALD患者的肿瘤坏死因子-α（TNF-α，p < 0.05）、白细胞介素-6（IL-6，p < 0.0001）、sICAM（p < 0.005）和sCD14（p < 0.0005）均显著升高，而肝硬化ALD患者的IL-10（p < 0.05）升高。除IL-10外，细胞因子之间以及与sICAM-1之间相互关联。内毒素、ENC和sCD14之间以及它们与细胞因子和sICAM-1之间均无相关性。内毒素水平升高与急性过量饮酒有关。未观察到性别差异。
急性酒精中毒而非严重的ALD导致显著的内毒素血症。血浆中和肝损伤中内毒素的能力有限似乎是ALD的一个重要因素，这可能是内毒素诱导的介质（如细胞因子以及与ALD发病机制相关的s-ICAM-1）释放的原因。
