Wallace J L, McKnight W, Asfaha S, Liu D Y
Intestinal Disease Research Unit, University of Calgary, Alberta, Canada.
Am J Physiol. 1998 May;274(5):G802-8. doi: 10.1152/ajpgi.1998.274.5.G802.
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.
中性粒细胞被认为是炎症性肠病中组织损伤的主要促成因素。在本研究中，我们评估了一种中性粒细胞激活和黏附抑制剂NPC-18915（4-｛2-[2-(2-苯并呋喃基)苯基]-(E)-乙烯基｝苯甲酸钠盐）在急性和复发性结肠炎模型中的作用。急性结肠炎通过结肠内给予半抗原诱导。在其他大鼠中，急性结肠炎发作6周后，通过皮下给予半抗原使结肠炎复发。在急性结肠炎诱导后的前4天给予NPC-18915可显著减轻组织损伤以及腹泻和粘连的发生率。当在结肠炎牢固确立后（半抗原注射后48小时）开始给予NPC-18915治疗时，未产生显著效果。NPC-18915在复发性结肠炎模型中能有效显著减轻结肠损伤和粒细胞浸润，在用抗中性粒细胞血清治疗的大鼠中也可观察到类似效果。这些结果表明，中性粒细胞激活抑制剂在急性和复发性结肠炎中均有效，尽管在前一种情况下，仅在结肠炎完全确立前给予药物时才有效。这些结果还表明，中性粒细胞是大鼠半抗原诱导性结肠炎的关键效应细胞，尤其是在复发性结肠炎的情况下。
