In inflammatory bowel disease (IBD), tumor necrosis factor plays an important role in mediating inflammation, but several other pathways are also involved in eliciting an inflammatory response. One such pathway is the invasion of the intestinal mucosa by leukocytes. Leukocytes within the systemic circulation move to sites of inflammation, and blocking this pathway could be an important treatment strategy for IBD. Anti-integrin therapy blocks the action of integrin on the surface of circulating immune cells and endothelial cell adhesion molecules, thereby inhibiting the interactions between leukocytes and intestinal blood vessels. Natalizumab, which acts on α4-integrin, was the first such drug to be approved for Crohn's disease, but its use is limited due to the risk of progressive multifocal leukoencephalopathy. Vedolizumab produces few systemic adverse effects because it acts on gut-trophic α4β7 integrin, and has been approved and is being used to treat IBD. Currently, several anti-integrin drugs, including etrolizumab, which acts on β7-integrin, and PF-00547569, which targets mucosal addressin cell adhesion molecule-1, are undergoing clinical trials and the results are being closely watched.

中文翻译：

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抗整合素治疗炎症性肠病。

在炎症性肠病（IBD）中，肿瘤坏死因子在介导炎症中起着重要作用，但其他几种途径也参与引起炎症反应。一种这样的途径是白细胞侵袭肠粘膜。全身循环中的白细胞移至炎症部位，阻断该途径可能是IBD的重要治疗策略。抗整合素疗法可阻断整合素在循环免疫细胞和内皮细胞粘附分子表面的作用，从而抑制白细胞与肠血管之间的相互作用。作用于α4-整联蛋白的那他珠单抗是第一种被批准用于克罗恩病的此类药物，但由于进行性多灶性白质脑病的风险，其使用受到限制。维多珠单抗几乎不产生全身性不良反应，因为它作用于肠道营养型α4β7整联蛋白，并且已经被批准用于治疗IBD。目前，数种抗整合素药物，包括作用于β7整合素的埃特罗珠单抗和靶向黏膜地址蛋白细胞粘附分子-1的PF-00547569，正在临床试验中，结果受到密切关注。