Medical Clinic 1, University of Erlangen-Nuremberg, Erlangen, Germany.
Dig Dis. 2010;28(3):386-94. doi: 10.1159/000320392. Epub 2010 Sep 30.
Uncontrolled activation of mucosal effector cells has been identified as the main pathogenic mechanism involved in the initiation and perpetuation of mucosal inflammation in inflammatory bowel diseases (IBD). The sustained activation of these cells leads to the aberrant production of various pro-inflammatory mediators, which co-ordinated action amplifies the inflammatory process. In this setting a network of tissue-specific chemoattractant cytokines (chemokines) and their corresponding receptors have been implicated as main contributors in the initiation and perpetuation of the inflammatory reaction in IBD. They are produced by a variety of inflammatory cells present in IBD lesions, as well as endothelial and epithelial cells. Chemokines not only control the multistep process of leukocyte adhesion to and migration across the endothelium, but also the release of lipid mediators and oxygen radicals from leukocytes, the modulation of tumorigenesis, release of matrix metalloproteinases and tissue fibrosis. Numerous data indicate that that intestinal chemokine expression is non-selectively up-regulated in IBD and correlates with disease activity. The development of selective inhibitors for chemokines or chemokine receptors, based on a more complete understanding of the immunopathogenic role of chemokines in intestinal inflammation, will be of great interest as potential novel therapeutic strategies in IBD.
黏膜效应细胞的失控激活已被确定为炎症性肠病（IBD）中黏膜炎症的起始和持续的主要致病机制。这些细胞的持续激活导致各种促炎介质的异常产生，它们的协同作用放大了炎症过程。在这种情况下，一系列组织特异性趋化因子（chemokines）及其相应的受体被认为是 IBD 中炎症反应起始和持续的主要因素。它们由 IBD 病变中存在的各种炎症细胞以及内皮细胞和上皮细胞产生。趋化因子不仅控制白细胞黏附到内皮细胞和穿过内皮细胞的多步过程，还控制白细胞释放脂质介质和氧自由基、调节肿瘤发生、释放基质金属蛋白酶和组织纤维化。大量数据表明，IBD 中肠道趋化因子的表达非选择性地上调，并与疾病活动相关。基于对趋化因子在肠道炎症中的免疫发病作用的更全面理解，开发针对趋化因子或趋化因子受体的选择性抑制剂将成为 IBD 中潜在的新型治疗策略。
