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

Abstract

BACKGROUND/AIMS:

Elevated concentrations of tumor necrosis factor receptors have been detected in alcoholic cirrhosis, but it remains unknown whether or not peripheral blood mononuclear cells are a source of tumor necrosis factor receptors and reflect the clinical disease activity of patients with advanced alcoholic liver disease.

METHODS:

Twenty-two abstinent patients in different stages of alcohol-induced cirrhosis according to the criteria of the Child-Pugh classification (Child-Pugh stage A: 4, Child-Pugh stage B: 10, Child-Pugh stage C: 8) were compared with four healthy individuals. Semi-quantitative reverse transcriptase-polymerase chain reaction was used for the measurement of the expression of tumor necrosis factor-alpha, soluble tumor necrosis factor receptors-p55, -p75, interleukin-10 and inducible nitric oxide synthase in unstimulated peripheral blood mononuclear cells.

RESULTS:

Unstimulated peripheral blood mononuclear cells of patients with alcoholic 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-receptors-p55/-p75 is significantly higher in patients with severe alcoholic cirrhosis (Child-Pugh stage B or C patients) than healthy controls (p<0.05), while peripheral blood mononuclear cells from patients with Child-Pugh stage A show a similiar pattern of gene expression to healthy controls. No significant up-regulation 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 with severe alcoholic cirrhosis (Child-Pugh stage B and C) demonstrate a systemic leukocyte activation and gene expression of tumor necrosis factor-alpha and tumor necrosis factor receptors-p55/-p75, which is correlated with the activity of the disease. Our data confirm previous studies that reported a correlation between plasma levels of pro-inflammatory cytokines and the severity of alcoholic cirrhosis. The role of interleukin-10 and inducible nitric oxide synthase in the pathogenesis of alcoholic cirrhosis remains to be fully elucidated.

• Authors: C Hanck, M Glatzel, M V Singer, S Rossol
• Journal: Journal of hepatology (J Hepatol) Vol. 32 Issue 1 Pg. 51-7 (Jan 2000) ISSN: 0168-8278 [Print] Netherlands
• PMID: 10673067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• DNA Primers
• Endotoxins
• RNA, Messenger
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• Receptors, Tumor Necrosis Factor, Type II
• Tumor Necrosis Factor-alpha
• Interleukin-10
• NOS2 protein, human
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II

Topics

• Antigens, CD (blood, genetics)
• DNA Primers (chemistry)
• Endotoxins (blood)
• Female
• Gene Expression
• Humans
• Interleukin-10 (genetics)
• Liver Cirrhosis, Alcoholic (blood, pathology)
• Male
• Middle Aged
• Monocytes (metabolism)
• Nitric Oxide Synthase (genetics)
• Nitric Oxide Synthase Type II
• RNA, Messenger (metabolism)
• Receptors, Tumor Necrosis Factor (blood, genetics)
• Receptors, Tumor Necrosis Factor, Type I
• Receptors, Tumor Necrosis Factor, Type II
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics)