Endotoxemia contributes to the immune paralysis in patients with cirrhosis

J Hepatol. 2007 May;46(5):816-26. doi: 10.1016/j.jhep.2006.12.018. Epub 2007 Feb 5.

Abstract

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 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers / blood
  • Cells, Cultured
  • Endotoxemia / blood
  • Endotoxemia / immunology*
  • Female
  • HLA-DR Antigens / blood*
  • HLA-DR Antigens / drug effects
  • HLA-DR Antigens / immunology
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology*
  • In Vitro Techniques
  • Interleukin-10 / blood
  • Lipopolysaccharides / administration & dosage
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / immunology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology
  • Reference Values
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Biomarkers
  • HLA-DR Antigens
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10