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

基本信息

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

项目摘要

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

在严重的酒精肝灾害中评估了与内毒素和细胞因子有关的巨噬细胞功能。临床研究：对酒精性肝灾害患者进行了预后因素。患有严重酒精性肝疾病（严重的酒精性肝炎或肝硬化的酒精性肝炎）的非生病性表现出严重的高胆红素血症，肝生物合成能力降低，明显的急性炎症反应显着，并产生了使用多重细胞型（MOF），例如散发性静脉内的危险范围（DIS）（DISERAILT）（DISERAID）（DIS）。模型显示血清CRP和DIC作为重要的独立预后因素。所有患者的血浆内毒素均升高，在非生存中注意到IL-6，IL-8和IL-L0的明显升高。在这些实验研究中，外周血单核细胞中阳性CDL4细胞的百分比增加：1）添加乙醇会抑制FITC标记的内毒素B的摄取……更多的y kupffer细胞，但不会影响肝细胞。 2）在给定硫乙酰氨酰胺的肝硬化大鼠中，肝脏的鲑鱼内毒素清除延迟。脾脏，肾脏和血液中的内毒素量更大，粪便中的毒素量较小。血清总胆红素，AST，ALT，LDH，BUN，肌酐和tnf- alphabere更高，凝血酶蛋白在cirrhotic大鼠中注射鲑鱼内毒素后的时间较低，而不是控制大鼠。盐酸盐内毒素的摄取和Tnf-字母的分泌得到了改善，脾巨噬细胞和外周血单核细胞的kupffer细胞得到了改善。cirrhotic Rats.tnf-tnf-alphasecortion-未经刺激的kupffer细胞和e coli氧化毒素的细胞受到了kupfffffffffffffffffff事孔。这些大鼠中e coli内毒素刺激的肺泡巨噬细胞的TNF降压显着增加。这些结果表明，严重肝病患者的内毒素清除通常被过度刺激，这可能导致细胞因子过度分泌，最后导致MOF的发展。较少的