Christoph Hanck

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 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.

Cytokine gene expression in peripheral blood mononuclear cells reflects a systemic immune response in alcoholic chronic pancreatitis

SummaryBackground. Recent data provide evidence of a systemic inflammatory response in severe acute pancreatitis; in contrast, the exact immune mechanisms underlying chronic pancreatitis remain unclear. Methods. To investigate the immune response in the clinical features of chronic pancreatitis, we investigated the gene expression of tumor necrosis factor-α (TNF-α), tumor necrosis factor receptor (TNFR)-p55 and -p75 and inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cells (PBMC) of 18 patients with late-stage alcoholic chronic pancreatitis of different disease activity (Balthazar criteria). Results. Semiquantitative reverse transcriptase-polymerase chain reaction revealed a significantly enhanced gene expression of TNF-α (P<0.005), TNFR-p55 (P<0.05) and TNFR-p75 (P<0.01) in unstimulated PBMC of patients with advanced chronic pancreatitis (11/18 with calcifications) compared to healthy controls (n=8). No significant difference was found between patients with mild acute pancreatitis and patients with an inactive quiescent pancreatitis. Moreover, no expression of inducible nitric oxide synthase was detectable. Conclusions. The enhanced gene expression of TNFR-p75, TNFR-p55 and TNF-α in unstimulated PBMC demonstrates an enhanced leucocyte activation in patients with late-stage chronic pancreatitis and suggests a pathogenetic role of the cytotoxic TNF-α pathway in the clinical features of alcoholic chronic pancreatitis. The pathogenetic role of nitric oxide in chronic pancreatitis remains to be fully elucidated.