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

Background. Recent data provide evidence of a systemic inflammatory respons e in severe acute pancreatitis; in contrast, the exact immune mechanisms un derlying chronic pancreatitis remain unclear, Methods. To investigate the immune response in the clinical features of chr onic pancreatitis, we investigated the gene expression of tumor necrosis fa ctor-alpha (TNF-alpha), 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 r evealed a significantly enhanced gene expression of TNF-alpha (P < 0.05), T NFR-p55 (P < 0.05) and TNFR-p75 (P < 0.01) in unstimulated PBMC of patients with advanced chronic pancreatitis ( 11/18 with calcifications) compared t o healthy controls (n = 8). No significant difference was found between pat ients with mild acute pancreatitis and patients with an inactive quiescent pancreatitis. Moreover, no expression of inducible nitric oxide synthase wa s detectable. Conclusions. The enhanced gene expression of TNFR-p75, TNFR-p55 and TNF-alp ha in unstimulated PBMC demonstrates an enhanced leucocyte activation in pa tients with late-stage chronic pancreatitis and suggests a pathogenetic rol e of the cytotoxic TNF-alpha pathway in the clinical features of alcoholic chronic pancreatitis. The pathogenetic role of nitric oxide in chronic panc reatitis remains to be fully elucidated.