Delayed neutrophil apoptosis is a feature of persistent acute inflammation.
Neutrophil-mediated damage has been shown to be associated with the develo
pment of inflammatory bowel disease (IBD). Persistence of these cells both
at the colonic site and circulation may further contribute to IBD. The aims
of this study were to determine whether neutrophils isolated from IBD pati
ents delay apoptosis and to investigate possible mechanisms involved in thi
s delay. We studied 20 patients with IBD, 13 with Crohn's disease, and 7 wi
th ulcerative colitis, all of whom were undergoing intestinal resection for
symptomatic disease. Seventeen patients undergoing elective resection of c
olon cancer acted as operative controls. Systemic, mesenteric arterial, and
mesenteric venous blood was harvested. Neutrophils isolated from patients
with IBD showed decreased spontaneous apoptosis compared to cancer patients
. Mesenteric venous serum of IBD patients contributed to this delay, which
contained higher concentrations of interleukin-8 (IL-8). Pro-caspase 3 expr
ession was also reduced in IBD neutrophils, which may contribute to decreas
ed spontaneous and Pas antibody-induced apoptosis. Neutrophil apoptosis may
be altered in Crohn's disease and ulcerative colitis through release of an
ti-apoptotic cytokines and altered caspase expression. The alterations in c
ell death mechanisms may lead to persistence of the inflammatory response a
ssociated with IBD.