title: Cytotoxic cells are activated in cellular infiltrates of alcoholic chronic pancreatitis.
abstract: OBJECTIVE
  Perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. In this study, the contribution of cell-mediated cytotoxicity in the pathogenesis of alcoholic chronic pancreatitis is assessed.
  
  
  METHODS
  Tissue sections of patients with alcoholic chronic pancreatitis were analyzed for perforin mRNA expression by in situ hybridization. In a further step, the phenotype and the relative frequency of perforin mRNA-expressing cells were determined.
  
  
  RESULTS
  In the normal pancreas, perforin mRNA-expressing cells are rarely present (mean, 0.3 cells/mm2). In contrast, the frequency of perforin mRNA-expressing cells is increased severalfold in diseased tissue specimens (mean, 6.6 cells/mm2). The frequency of perforin mRNA-expressing cells is high in the CD56+ (18%) and CD8+ cell population (12%) but low in the CD4+ cell population (1%).
  
  
  CONCLUSIONS
  The significantly elevated frequencies of perforin mRNA-expressing cells in the pancreas of patients with alcoholic chronic pancreatitis suggest an involvement of cell-mediated cytotoxicity in the pathogenesis of this disease. The preferential localization of these activated cells close to areas with parenchyma provides circumstantial evidence that autoreactive cytotoxic cells may contribute to tissue destruction in alcoholic chronic pancreatitis.
authors.affiliation: Department of Pathology, University of Bern, Switzerland.
authors.forename: R E
authors.initials: RE
authors.lastname: Hunger
authors.forename: C
authors.initials: C
authors.lastname: Mueller
authors.forename: K
authors.initials: K
authors.lastname: Z'graggen
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: M W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D002469:Cell Separation; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000473:pathology* / Q000503:physiopathology*; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin