Endotoxemia contributes to the immune paralysis in patients with cirrhosis

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)-α 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 (r2 = 0.2642; p = 0.008) and serum interleukin-10 (IL-10) (r2 = 0.2167; p = 0.019) in patients with Child-Pugh class C. Serum endotoxin level was in linear relationship to serum IL-10 level (r2 = 0.1868; p = 0.002) and HLA-DR expression (r2 = 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.