Gene expression of TNF-receptors in peripheral blood mononuclear cells of patients with alcoholic cirrhosis

Background/Aims:Elevated concentrations of tumor necrosis factor receptors have been detected in alcoholic cirrhosis, but it remains unknown whether o r not peripheral blood mononuclear cells are a source of tumor necrosis fac tor receptors and reflect the clinical disease activity of patients with ad vanced alcoholic liver disease. Methods: Twenty;two abstinent patients in different stages of alcohol-induc ed cirrhosis according to the criteria of the Child-Pugh classification (Ch ild-Pugh stage A: 4, Child-Pugh stage B: 10, Child-Pugh stage C: 8) were co mpared with four healthy individuals. Semi-quantitative reverse transcripta se-polymerase chain reaction was used for the measurement of the expression of tumor necrosis factor-alpha, soluble tumor necrosis factor receptors-p5 5, -p75, interleukin-10 and inducible nitric oxide synthase in unstimulated peripheral blood mononuclear cells. Results: Unstimulated peripheral blood mononuclear cells of patients with a lcoholic cirrhosis demonstrate a stage-dependent enhanced RNA expression of tumor necrosis factor-alpha (healthy controls 0/4, Child-Pugh stage A 2/4, stage B 10/10, stage C 8/8; p<0.01). The mRNA expression of TNF-receptorsp 55/-p75 is significantly higher in patients with severe alcoholic cirrhosis (Child-Pugh stage B or C patients) than healthy controls (p<0.05), while p eripheral blood mononuclear cells from patients with Child-Pugh stage A sho w a similiar pattern of gene expression to healthy controls. No significant upregulation of interleukin-10 was found. Inducible nitric oxide synthase was detectable in Child-Pugh stage C (p<0.05). Conclusions: Unstimulated peripheral blood mononuclear cells of patients wi th severe alcoholic cirrhosis (Child-Pugh stage B and C) demonstrate a syst emic leukocyte activation and gene expression of tumor necrosis factor-alph a and tumor necrosis factor receptors-p55/-p75, which is correlated with th e activity of the disease. Our data confirm previous studies that reported a correlation between plasma levels of pro-inflammatory cytokines and the s everity of alcoholic cirrhosis. The role of interleukin-10 and inducible ni tric oxide synthase in the pathogenesis of alcoholic cirrhosis remains to b e fully elucidated.