Endotoxemia contributes to the immune paralysis in patients with cirrhosis

被引:139
作者
Lin, Chun-Yen
Tsai, I-Fan
Ho, Yu-Pin
Huang, Ching-Tai
Lin, Yung-Chang
Lin, Chun-Jung
Tseng, Shu-Chin
Lin, Wei-Pin
Chen, Wei-Ting
Sheen, I-Shyan [1 ]
机构
[1] Chang Gung Univ, Chang Gung Mem Hosp, Linkou Med Ctr, Dept Hepatogastroenterol, Tao Yuan, Taiwan
[2] Chang Gung Univ, Chang Gung Mem Hosp, Linkou Med Ctr, Dept Internal Med, Tao Yuan, Taiwan
关键词
HLA-DR antigen (human leukocyte antigen-DR); immune paralysis; interleukin-10; tumor necrosis factor-alpha; endotoxin;
D O I
10.1016/j.jhep.2006.12.018
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Immune paralysis, defined as decreased HLA-DR expression on monocytes and indicated immune dysfunctions, was found in sepsis, severe acute pancreatitis and acute liver failure. However, the relationship between HLA-DR expression and cirrhosis is unclear. Methods:We enrolled 64 patients with liver cirrhosis and 23 healthy volunteers. HLA-DR expressions, functions of monocyte, serum cytokines and endotoxin levels were measured. Results: Compared to healthy volunteers, HLA-DR expressions were significantly lower in Child-Pugh class C cirrhotic patients (89.28% vs 69.29%, p < 0.001). These low-HLA-DR-expressed monocytes were with decreased ability of tumor necrosis factor (TNF)-alpha secretion, decreased expression of inducible nitric oxide synthetase (NOS) and decreased allo-stimulatory ability but normal phagocytosis ability. The co-stimulatory molecules like CD40 and CD86 were down-regulated as well but not CD80. Furthermore, HLA-DR expression was linearly correlated with the presence of hepatic encephalopathy (r(2) = 0.2642; p = 0.008) and serum interleukin-10 (IL-10) (r(2) = 0.2167; p = 0.019) in patients with Child-Pugh class C. Serum endotoxin level was in linear relationship to serum IL-10 level (r(2) = 0.1868; p = 0.002) and HLA-DR expression (r(2) = 0.0924; p = 0.036). In addition, endotoxin, mediated by IL-10, could down-regulate the HLA-DR expression. Conclusions: Child-Pugh class C cirrhotic patients suffer from down-regulation of HLA-DR expression. Endotoxemia, possibly mediated by IL-10, contributes to this HLA-DR down-regulation. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:816 / 826
页数:11
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