• Chun-Yen Lin, I-Fan Tsai, Yu-Pin Ho, Ching-Tai Huang, Yung-Chang Lin, Chun-Jung Lin, Shu-Chin Tseng, Wei-Pin Lin, Wei-Ting Chen, and I-Shyan Sheen.
• Department of Hepatogastroenterology, Linkou Medical Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
• J. Hepatol. 2007 May 1; 46 (5): 816-26.

Background/AimsImmune 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.MethodsWe enrolled 64 patients with liver cirrhosis and 23 healthy volunteers. HLA-DR expressions, functions of monocyte, serum cytokines and endotoxin levels were measured.ResultsCompared 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 (iNOS) 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.ConclusionsChild-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.

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