Macrophage functions in severe liver disturbance and multiple organ failure

在严重酒精性肝损害中评价与内毒素和细胞因子相关的巨噬细胞功能。临床研究：研究酒精性肝病患者的预后因素。死亡的重度酒精性肝病（重度酒精性肝炎或酒精性肝炎合并肝硬化）患者表现为严重的高胆红素血症、肝脏生物合成能力降低、急性炎症反应明显，并发生多器官功能衰竭（MOF），如弥散性血管内凝血（DIC）或肾功能衰竭，考克斯比例风险模型多因素分析显示血清CRP和DIC是显著的独立预后因素。所有患者血浆内毒素水平均升高，死亡患者IL-6、IL-8和IL-10水平明显升高。外周血单核细胞中CD_（14）阳性细胞百分率增高。实验研究：1）乙醇抑制FITC标记内毒素B的摄取 ...更多信息 y枯否细胞，但不影响肝细胞。2)在给予硫代乙酰胺的哮喘大鼠中，肝脏对沙门氏菌内毒素的清除延迟。脾、肾和血液中的内毒素量较多，粪便中的内毒素量较少。实验组大鼠注射沙门氏菌内毒素后，血清总胆红素、AST、ALT、LDH、BUN、肌酐、TNF-α均明显高于对照组，而凝血酶原时间明显低于对照组。结果表明，内毒素血症大鼠Kupffer细胞摄取内毒素和分泌TNF-α的能力降低，脾巨噬细胞和外周血单核细胞分泌TNF-α的能力增强，未受内毒素刺激的Kupffer细胞和大肠杆菌内毒素刺激的Kupffer细胞分泌TNF-α的能力降低。结果表明，在严重肝病患者中，巨噬细胞由于清除内毒素而受到过度刺激，导致细胞因子分泌过多，最终导致MOF的发生。少

Macrophage function related to endotoxin and cytokines was evaluated in severe alcoholic liver disturbance. Clinical studies : Prognostic factors were studied in patients with alcoholic liver disturbances. Nonsurvivors with severe alcoholic liver diseases (severe alcoholic hepatitis or alcoholic hepatitis with cirrhosis) showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure (MOF), such as disseminated intravascular coagulation (DIC) or renal failure.Multivariate analysis using Cox proportional hazards model showed serum CRP and DIC as significant independent prognostic factors. Plasma endotoxin was elevated in all patients and marked elevations of IL-6, IL-8 and IL-l0 were noted in nonsurvivors. The percentage of positive CDl4 cells in peripheral blood monocytes was increaed in these patients. Experimental studies : 1) An addition of ethanol inhibited the uptake of FITC-labelled endotoxin b … More y Kupffer cells but did not affect that by hepatocytes. 2) In cirrhotic rats given thio-acetamide, the clearance of Salmonela endotoxin by the liver was delayed. The amount of endotoxin in the spleen, kidney and blood was larger and that excreted in the stool was smaller. Serum total bilirubin, AST, ALT, LDH, BUN, creatinine and TNF- alphawere higher and prothrombin time was lower after the injection of Salmonela endotoxin in cirrhotic rats than those in control. The uptake of Salmonela endotoxin and the secretion of TNF- alphaby the Kupffer cells were decreased and those by the splenic macrophages and the peripheral blood monocytes were increaed in cirrhotic rats.TNF- alphasecretion from unstimulated Kupffer cells and E coli endotoxin-stimulated Kupffer cells were decreased. TNF- alphasecretion from E coli endotoxin-stimulated alveolar macrophages were markedly increaed in these rats.These results suggest that macrophages are generally overstimulated for endotoxin clearance in patients with severe liver diseases, which may lead to the oversecretion of cytokines and finally to the development of MOF. Less