Jl. Wallace et al., REDUCTION OF ACUTE AND REACTIVATED COLITIS IN RATS BY AN INHIBITOR OFNEUTROPHIL ACTIVATION, American journal of physiology: Gastrointestinal and liver physiology, 37(5), 1998, pp. 802-808
Neutrophils have been implicated as major contributors to tissue injur
y in inflammatory bowel disease. In this study, we have assessed the e
ffects of an inhibitor of neutrophil activation and adherence, NPC-189
15 -{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, col
itis was reactivated 6 mk after a bout of acute colitis by subcutaneou
s administration of the hapten. NPC-18915 given during the first 4 day
s after induction of acute colitis significantly reduced tissue injury
and the incidence of diarrhea and adhesions. When treatment of NPC-18
915 was initiated after colitis was firmly established (48 h posthapte
n), it did not produce a significant effect. NPC-18915 was effective a
t significantly reducing colonic injury and granulocyte infiltration i
n the reactivated colitis model, and a similar effect could be observe
d 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 i
s only seen when the drug is given before full establishment of coliti
s. These results also suggest that neutrophils are a critical effector
cell of hapten-induced colitis in the rat, particularly in the case o
f reactivated colitis.