REDUCTION OF ACUTE AND REACTIVATED COLITIS IN RATS BY AN INHIBITOR OFNEUTROPHIL ACTIVATION

Citation
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
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
ISSN journal
0193-1857
Volume
37
Issue
5
Year of publication
1998
Pages
802 - 808
Database
ISI
SICI code
0193-1857(1998)37:5<802:ROAARC>2.0.ZU;2-D
Abstract
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.