Endotoxemia contributes to the immune paralysis in patients with cirrhosis.
OBJECTIVE
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 (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.


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.
Lin
Chun-Yen
CY
Department of Hepatogastroenterology, Linkou Medical Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
Tsai
I-Fan
IF
Ho
Yu-Pin
YP
Huang
Ching-Tai
CT
Lin
Yung-Chang
YC
Lin
Chun-Jung
CJ
Tseng
Shu-Chin
SC
Lin
Wei-Pin
WP
Chen
Wei-Ting
WT
Sheen
I-Shyan
IS
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D019446:Endotoxemia / Q000097:blood / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D012016:Reference Values; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10