EVALUATION OF THE ROLE OF NEUTROPHILS IN THE PATHOGENESIS OF ACETIC ACID-INDUCED COLITIS IN MICE

Background: Neutrophils are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD) such as ulcerative colitis and C rohn's disease, since prominent neutrophil infiltration has been obser ved in the inflamed colonic mucosa of patients with IBD. However, the role of neutrophils in the pathogenesis of IBD and experimental coliti s remains equivocal. The aim of the present study is to clarify the po ssible role of neutrophils in the progression of acetic acid-induced c olitis in mice. Methods: Using neutropenic mice treated with cyclophos phamide or with an LTB4 receptor antagonist, ONO-4057, the relationshi p between the severity of macroscopic colonic damage, the extent of my eloperoxidase (MPO) activities in the colonic tissues, and the number of neutrophils in the blood were examined after induction of colitis i n mice. Results: Changes of MPO activity in the colonic tissues parall eled well with the severity of the mucosal damage. In spite of a signi ficant reduction in the number of neutrophils in the blood in cyclopho sphamide-treated mice, neither the severity of mucosal damage in the c olon nor the increase in MPO activities in the colonic tissues was aff ected 24 h after induction of colitis. Treatment with ONO-4057 signifi cantly suppressed both the severity of mucosal damage in the colon and MPO activities in the colonic tissues in acetic acid-induced colitis in mice. Conclusions: The present results, obtained using treatment wi th cyclophosphamide and ONO-4057, show that the severity or the progre ssion of acetic acid-induced colitis in mice was not influenced by a r eduction of circulating neutrophils to about 25% of base line.