Macrophage functions in severe liver disturbance and multiple organ failure

巨噬细胞在严重肝功能紊乱和多器官衰竭中的功能

• 批准号: 08670612
• 负责人: FUKUI Hiroshi
• 金额: $ 1.28万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670612/
• 关键词: endotoxin; alcohol; acute hepatic failure; liver cirrhosis; macrophage; tumor necrosis factor

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

重度酒精性肝病患者巨噬细胞功能与内毒素和细胞因子的关系临床研究：对酒精性肝障碍患者的预后因素进行了研究。严重酒精性肝病（严重酒精性肝炎或酒精性肝炎合并肝硬化）的非幸存者表现为严重的高胆红素血症，肝脏生物合成能力降低，明显的急性炎症反应，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。Cox比例风险模型多因素分析显示，血清CRP和DIC是重要的独立预后因素。所有患者血浆内毒素均升高，非幸存者血浆中IL-6、IL-8和il - 10均显著升高。这些患者外周血单核细胞中cd14阳性细胞的百分比增加。实验研究：1)添加乙醇可抑制Kupffer细胞对fitc标记内毒素的摄取，但对肝细胞的摄取无影响。2)肝硬化大鼠给予硫代乙酰胺后，肝脏对沙门氏菌内毒素的清除延迟。脾脏、肾脏和血液中的内毒素含量较多，而粪便中的内毒素含量较少。注射沙门氏菌内毒素后肝硬化大鼠血清总胆红素、AST、ALT、LDH、BUN、肌酐、TNF- α均高于对照组，凝血酶原时间低于对照组。肝硬化大鼠脾巨噬细胞和外周血单核细胞对沙门氏菌内毒素的吸收和TNF- α的分泌减少，而对沙门氏菌内毒素的吸收和TNF- α的分泌增加。未受刺激的Kupffer细胞和大肠杆菌内毒素刺激的Kupffer细胞的TNF- α相分泌减少。大肠杆菌内毒素刺激的肺泡巨噬细胞分泌TNF- α明显增加。这些结果表明，在严重肝病患者中，巨噬细胞通常被过度刺激以清除内毒素，这可能导致细胞因子的过度分泌，最终导致MOF的发生。少

项目成果

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H Fukui、T Tsujita、M Matsumoto 等人：慢性肝炎和肝硬化中的内毒素血症：副现象或病理相关性？