Neutrophils have been implicated as major contributors to tissue injury in
inflammatory bowel disease. In this study, we have assessed the effects of an inhibitor of neutrophil activation and adherence,
NPC-18915 (4-¿2-[2-(2-benzofuranyl)phenyl]-(E)-ethenyl¿benzoic
acid sodium salt), in models of both acute and reactivated
colitis. Acute
colitis was induced by intracolonic administration of a
hapten. In other rats,
colitis was reactivated 6 wk after a bout of acute
colitis by subcutaneous administration of the
hapten.
NPC-18915 given during the first 4 days after induction of acute
colitis significantly reduced tissue injury and the incidence of
diarrhea and adhesions. When treatment of
NPC-18915 was initiated after
colitis was firmly established (48 h posthapten), it did not produce a significant effect.
NPC-18915 was effective at significantly reducing colonic injury and granulocyte infiltration in the reactivated
colitis model, and a similar effect could be observed in rats treated with antineutrophil serum. These results demonstrate that an inhibitor of neutrophil activation is effective in both acute and reactivated
colitis, although in the former case, effectiveness is only seen when the
drug is given before full establishment of
colitis. These results also suggest that neutrophils, are a critical effector cell of
hapten-induced
colitis in the rat, particularly in the case of reactivated
colitis.