Higa A, McKnight G W, Wallace J L
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Eur J Pharmacol. 1993 Aug 3;239(1-3):171-6. doi: 10.1016/0014-2999(93)90990-y.
Intestinal epithelial permeability can be modulated by the immune system and can be greatly increased by transepithelial migration of neutrophils. Since immunosuppressants have been reported to inhibit the ability of neutrophils to migrate, we assessed the effects of two immunosuppressants on epithelial permeability and granulocyte infiltration in a model of acute colitis. Epithelial permeability was measured at 3 and 6 h after induction of colitis in the rabbit by intracolonic administration of trinitrobenzene sulfonic acid. At these times, blood-to-lumen leakage of 51Cr-EDTA was elevated by approximately 8- and 18-fold, respectively, above levels observed in healthy controls. Pretreatment with either of the immunosuppressants (cyclosporin A and L-683,590) significantly reduced the changes in 51Cr-EDTA leakage observed at the latter time point. These drugs also significantly attenuated granulocyte infiltration of the colon after induction of colitis, as measured by tissue myeloperoxidase activity. Unlike the immunosuppressants, misoprostol, a prostaglandin analogue, attenuated the increases in colonic permeability but had no effect on granulocyte infiltration in this model. These results demonstrate that two structurally unrelated immunosuppressants are capable of markedly reducing neutrophil infiltration and the colonic permeability changes observed in an experimental model of acute colitis, although the mechanisms through which these effects are produced remain unclear.
肠道上皮通透性可受免疫系统调节，中性粒细胞经上皮迁移可使其大幅增加。由于有报道称免疫抑制剂可抑制中性粒细胞的迁移能力，我们在急性结肠炎模型中评估了两种免疫抑制剂对上皮通透性和粒细胞浸润的影响。通过结肠内给予三硝基苯磺酸诱导家兔结肠炎，在诱导后3小时和6小时测量上皮通透性。此时，51Cr - EDTA从血液到肠腔的渗漏量分别比健康对照中观察到的水平升高了约8倍和18倍。用任何一种免疫抑制剂（环孢素A和L - 683,590）预处理均显著降低了在后者时间点观察到的51Cr - EDTA渗漏变化。通过组织髓过氧化物酶活性测定，这些药物还显著减轻了结肠炎诱导后结肠的粒细胞浸润。与免疫抑制剂不同，前列腺素类似物米索前列醇减轻了结肠通透性的增加，但对该模型中的粒细胞浸润没有影响。这些结果表明，两种结构不相关的免疫抑制剂能够显著减少急性结肠炎实验模型中观察到的中性粒细胞浸润和结肠通透性变化，尽管产生这些作用的机制仍不清楚。
