Increase in colorectal epithelial apoptotic cells in patients with ulcerative colitis ultimately requiring surgery

BACKGROUND AND AIMS: Up to one-third of patients with ulcerative colitis (UC) need to undergo surgery, but the factors that exacerbate inflammation remain unclear. The authors hypothesize that excessive apoptosis reported in active UC may disrupt epithelial defenses and exacerbate the disease. The aim of the present study was to clarify whether apoptotic epithelial cells and histiocytes engulfing them increased in patients with active UC who ultimately require surgery (UC-S) rather than those receiving medication alone (UC-M). METHODS: The study included 29 patients with UC-S, 35 with UC-M, 18 with infectious colitis, and 16 healthy controls. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Using biopsy specimens taken from the most severely inflamed rectosigmoid mucosa as determined endoscopically, the apoptotic index (apoptotic cells/epithelial cells,%) and density (per mm2) of lamina propria histiocytes positive for CD68 were then evaluated. Statistical differences were tested with the Mann-Whitney U-test. RESULTS: The apoptotic indices in UC-M patients were significantly higher than those in controls (P < 0.05) but almost equal to those in infectious colitis patients. In the upper and lower halves of the mucosa, both apoptotic indices and histiocyte densities were significantly higher for UC-S than in UC-M (P < 0.01). Ratios of the mean apoptotic index for UC-S to that for UC-M exceeded 3.4, while ratios of the mean histiocyte density were limited to approximately 1.6. CONCLUSIONS: The results suggest that epithelial apoptosis is a non-specific phenomenon and that an increased number of apoptotic cells exceeding histiocyte phagocytic capacity may play a part in the disruption of epithelial defenses and further accelerate mucosal inflammation.