van Hogezand R A, Verspaget H W
Dept. of Gastroenterology and Hepatology, University Hospital Leiden, The Netherlands.
Scand J Gastroenterol Suppl. 1997;223:105-7.
In the past few years new concepts have been formulated for the therapeutic management of difficult-to-treat inflammatory bowel disease, based on better insights in the pathophysiological processes in inflamed colonic mucosa. TNF alpha, for example, has been shown to play a major role orchestrating several other cytokines and pathways in the immunological network. TNF alpha is a pro-inflammatory cytokine. In contrast, IL-10 is an anti-inflammatory cytokine. IL-10-deficient mice ('IL-10 knockout mice') will spontaneously develop enteritis in several parts of the digestive tract. Administration of IL-10 has been shown to improve and even to prevent the enteritis in these mice. One of the functions of IL-10 is to inhibit the TNF alpha production. Elimination of TNF alpha with anti-TNF alpha antibodies and administration of IL-10 is, therefore, thought to achieve healing of the inflamed mucosa in man as well. The first uncontrolled studies with intravenous administration of chimeric anti-TNF alpha antibodies and with human recombinant IL-10 are hopeful for the future management of patients with inflammatory bowel disease; particularly since a fast healing of colonic mucosa was demonstrated and no serious adverse events were described. One has to be aware, however, of allergic reactions to the 'foreign' peptide. Because of rapid fibrosing and scarring in a narrow lumen, e.g. the ileum, stenosis formation could take place. In one described case a surgical intervention was needed because of this complication. For the near future these new and potent drugs seem very promising, although at present they are only available for trials with Crohn's disease patients. Certainly, in the coming years more immunomodulating drugs will be developed for use in man.
在过去几年中，基于对炎症性结肠黏膜病理生理过程更深入的了解，针对难治性炎症性肠病的治疗管理已形成了新的概念。例如，肿瘤坏死因子α（TNFα）已被证明在免疫网络中协调其他几种细胞因子和信号通路方面发挥着主要作用。TNFα是一种促炎细胞因子。相比之下，白细胞介素10（IL - 10）是一种抗炎细胞因子。IL - 10基因缺陷小鼠（“IL - 10基因敲除小鼠”）会在消化道的几个部位自发发生肠炎。已证明给予IL - 10可改善甚至预防这些小鼠的肠炎。IL - 10的功能之一是抑制TNFα的产生。因此，用抗TNFα抗体消除TNFα以及给予IL - 10被认为也能实现人类炎症黏膜的愈合。最初关于静脉注射嵌合抗TNFα抗体和人重组IL - 10的非对照研究为炎症性肠病患者的未来治疗带来了希望；特别是因为已证明结肠黏膜能快速愈合且未描述有严重不良事件。然而，必须意识到对“外来”肽的过敏反应。由于在狭窄管腔（如回肠）中会迅速发生纤维化和瘢痕形成，可能会出现狭窄。在一个已报道的病例中，由于这种并发症需要进行手术干预。在不久的将来，这些新型强效药物似乎非常有前景，尽管目前它们仅可用于克罗恩病患者的试验。当然，在未来几年将会研发出更多用于人类的免疫调节药物。
