Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: Relation to severity of liver disturbance
Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: Relation to severity of liver disturbance
复制标题
DOI：
10.1111/j.1530-0277.2000.tb00012.x
复制
发表时间：
2000-04-01
影响因子：
3.2
通讯作者：
Fukui, H
中科院分区：
文献类型：
--
作者：
Fujimoto, M;Uemura, M;Fukui, H
背景：内毒素在酒精性肝病的发生和加重中起重要作用。在这项研究中，我们评估了酒精性肝炎患者急性期和恢复期的血浆内毒素水平和血清细胞因子及脂多糖结合蛋白（LBP）浓度;我们还探讨了与致死性结局相关的预后因素。14例患者，包括8例酒精性肝炎（AH），5例酒精性肝炎合并AH（LC+AH），和1例重度酒精性肝炎（SAH）。结果：急性期血浆内毒素水平在AH组（184.4 ± 159.4pg/ml）和LC+AH组（206.9 ± 174.9pg/ml）明显高于健康对照组（10.4 ± 5.5pg/ml，P < 0.001）;特别是，在一个SAH患者和两个非幸存者之一，血浆内毒素水平显着高于其他情况下。在大多数存活者中，血浆内毒素水平在恢复期下降，而在两个死亡者中的一个在终末期进一步升高。AH和LC+AH患者急性期血清白细胞介素（IL）-6和IL-8水平显著高于健康受试者。这些水平在死亡者和一例SAH患者中尤其高。ILIO在两名死亡者中增加，一名SAH患者和一名LC+AH患者。在恢复期，这些细胞因子水平在幸存者趋于下降，但在非幸存者，IL-6仍然很高，IL-8和IL-10进一步增加。所有患者的肿瘤坏死因子-α水平在整个过程中均低于检测限。血清脂多糖结合蛋白（LBP）普遍升高，在急性期和恢复期下降，在所有的幸存者，但在一个非幸存者，LBP明显升高，在终末期。在急性期，血浆内毒素水平与白色血细胞计数、中性粒细胞计数和血清IL-8呈正相关。IL-8与中性粒细胞计数呈正相关，与血清胆碱酯酶、促肝纤维化试验和血清白蛋白水平呈负相关。IL-6与白色细胞计数、中性粒细胞计数、C反应蛋白、血清总胆红素呈正相关，与肝促活素试验、血清总蛋白水平呈负相关。结论：内毒素血症及IL-8水平升高可能在酒精性肝炎患者中性粒细胞活化和迁移中起重要作用。炎性细胞因子IL-6和IL-8的显著升高与酒精性肝炎的严重程度和不良预后相关。血清LBP可作为酒精中毒患者炎症反应的一个指标。
Background: Endotoxin plays an important role in the initiation and aggravation of alcoholic liver disease. In this study, we evaluated plasma endotoxin levels and serum concentrations of cytokines and lipopolysaccharide binding protein (LBP) during the acute and recovery phase of patients with alcoholic hepatitis; we also explored the prognostic factors associated with a fatal outcome.Methods: Fourteen patients, consisting of eight patients with alcoholic hepatitis (AH), five cirrhotics with superimposed AH (LC+AH), and one patient with severe alcoholic hepatitis (SAH), were studied. Among these, two with LC+AH died of hepatic failure.Results: Plasma endotoxin levels in the acute phase were higher in patients with AH (184.4 +/- 159.4 pg/ml) and LC+AH (206.9 +/- 174.9 pg/ml) than in healthy subjects (10.4 +/- 5.5 pg/ml, p < 0.001). In particular, in one patient with SAH and one of two nonsurvivors, plasma endotoxin levels were markedly high relative to the other cases. In most survivors, plasma endotoxin levels decreased in the recovery phase, whereas they further increased at the terminal stage in one of two nonsurvivors Serum interleukin (IL)-6 and IL-8 levels in the acute phase were significantly higher in patients with AH and LC+AH as compared with healthy subjects. These levels were especially high in nonsurvivors and in one patient with SAH. ILIO increased in two nonsurvivors, one patient with SAH, and one with LC+AH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in nonsurvivors, IL-6 remained high, and IL-8 and IL-10 further increased. Tumor necrosis factor-alpha levels were below the detection limit throughout the course in all patients. Serum lipopolysaccharide binding protein (LBP) generally was elevated in the acute phase and decreased in the recovery phase in all survivors, but in one of the nonsurvivors, LBP was elevated markedly at the terminal stage. In the acute phase, plasma endotoxin levels were correlated positively with white blood cell counts, neutrophil counts, and serum IL-8. IL-8 was correlated positively with neutrophil counts and negatively with serum cholinesterase, hepaplastin test, and serum albumin levels. IL-6 was correlated positively with white blood cell and neutrophil counts, C-reactive protein, and serum total bilirubin and negatively with hepaplastin test and serum total protein levels. Serum LBP was correlated positively with white blood cell and neutrophil counts.Conclusions: Endotoxemia and related elevation of IL-8 may play an important role in the activation and migration of neutrophils in patients with alcoholic hepatitis. Marked elevation of inflammatory cytokines, IL-6 and IL-8, are related to severity and poor prognosis of alcoholic hepatitis. Serum LBP may serve as an index of inflammatory reaction in alcoholics.