CYTOTOXIC-CELLS ARE ACTIVATED IN CELLULAR INFILTRATES OF ALCOHOLIC CHRONIC-PANCREATITIS

Background & Aims: Perforin messenger RNA (mRNA) expression has been s hown to be a specific in vivo activation marker for cytotoxic cells. I n this study, the contribution of cell-mediated cytotoxicity in the pa thogenesis of alcoholic chronic pancreatitis is assessed. Methods: Tis sue sections of patients with alcoholic chronic pancreatitis were anal yzed for perforin mRNA expression by in situ hybridization. In a furth er step, the phenotype and the relative frequency of perforin mRNA-exp ressing cells were determined. Results: In the normal pancreas, perfor in mRNA-expressing cells are rarely present (mean, 0.3 cells/mm(2)). I n contrast, the frequency of perforin mRNA-expressing cells is increas ed severalfold in diseased tissue specimens (mean, 6.6 cells/mm(2)). T he frequency of perforin mRNA-expressing cells is high in the CD56(+) (18%) and CD8(+) cell population (12%) but low in the CD4(+) cell popu lation (1%). Conclusions: The significantly elevated frequencies of pe rforin mRNA-expressing cells in the pancreas of patients with alcoholi c chronic pancreatitis suggest an involvement of cell-mediated cytotox icity in the pathogenesis of this disease. The preferential localizati on of these activated cells close to areas with parenchyma provides ci rcumstantial evidence that autoreactive cytotoxic cells may contribute to tissue destruction in alcoholic chronic pancreatitis.