Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation

The mechanisms of tissue damage in ulcerative colitis anal Crohm's disease may reflect disordered humoral or cell-mediated effector mechanisms, respec tively. Mucosal biopsies from untreated inflammatory bowel disease patients and normal controls were analysed for the expression of granzyme B, a cyto toxic effector molecule specifically associated with cell-mediated immunity , and for regulatory cytokines, Messenger RNA (mRNA) was analysed by revers e transcription-polymerase chain reaction and enzyme-linked oligonucleotide chemiluminescence assay. Mucosal biopsies were analysed by immunohistochem istry for granzyme B protein and lymphocyte markers and for the presence of apoptotic cells by terminal deoxynucleotidyl transferase end labelling Gra nzyme B mRNA was elevated in Crohn's disease, but not in ulcerative colitis or control mucosal biopsies. Granzyme B mRNA levels correlated with interf eron gamma mRNA levels in Crohn's disease. Granzyme B was expressed in CD3, CD8+ T cells in the lamina propria of Crohn's disease mucosa and there we re significantly more apoptotic cells in the lamina propria in Crohn's dise ase. in conclusion, granzyme B-expressing T lymphocytes are present in the focal mucosal lesions of Crohn's disease, together with spatially related a poptotic cell death. These results support the hypothesis that T-cell-media ted cytotoxic effector mechanisms may play a role in Crohn's disease, Copyr ight (C) 2000 John Wiley & Sons, Ltd.