PDF(Pubmed)
Abstract：
Ulcerative colitis (UC) and Crohn\'s disease (CD) are part of Inflammatory Bowel Diseases (IBD) and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells. In addition, the main inflammatory mediator is related to the tumor necrosis factor-alpha (TNF-α). TNF-α is a me-diator of the intestinal inflammatory processes, thus being one of the main cytokines involved in the pathogenesis of IBD, however, its levels, when measured, are present in the serum of patients with IBD. In addition, TNF-α plays an important role in promoting inflammation, such as the production of interleukins (IL), for instance IL-1β and IL-6. There are two receptors for TNF as following: The tumor necrosis factor 1 receptor (TNFR1); and the tumor necrosis factor 2 receptor (TNFR2). They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity. The soluble TNF form binds to the TNFR1 receptor with, and its activation results in a signaling cascade effects such as apoptosis, cell proliferation and cytokine secretion. In contrast, the transmembrane TNF form can bind both to TNFR1 and TNFR2. Recent studies have suggested that TNF-α is one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD, since TNF levels are present in the serum of both patients with UC and CD. Intravenous and subcutaneous biologics targeting TNF-α have revolutionized the treatment of IBD, thus becoming the best available agents to induce and maintain IBD remission. The application of antibodies aimed at neutralizing TNF-α in patients with IBD that induce a satisfactory clinical response in up to 60% of patients, and also induced long-term maintenance of disease remission in most patients. It has been suggested that anti-TNF-α agents inactivate the pro-inflammatory cytokine TNF-α by direct neutralization, i.e., resulting in suppression of inflammation. However, anti-TNF-α antibodies perform more complex functions than a simple blockade.
摘要：
溃疡性结肠炎（UC）和克罗恩病（CD）是炎症性肠病（IBD）的一部分，具有肠坏死，肠神经元和肠胶质细胞等病理生理过程。此外,主要的炎症介质与肿瘤坏死因子-α（TNF-α）有关。TNF-α是肠道炎症过程的主要因素，是IBD发病的主要细胞因子之一,然而,其水平,当测量时，存在于IBD患者的血清中。此外,TNF-α在促进炎症反应中起重要作用,例如白细胞介素（IL）的产生，例如IL-1β和IL-6。有两种TNF受体如下:肿瘤坏死因子1受体(TNFR1);和肿瘤坏死因子2受体(TNFR2)。它们与IBD的发病机理有关，在IBD中已检测到它们的受体，它们的表达与疾病活动相关。可溶性TNF形式与TNFR1受体结合，它的激活导致信号级联效应，如细胞凋亡，细胞增殖和细胞因子分泌。相比之下,跨膜TNF形式可以与TNFR1和TNFR2结合。近年来的研究表明,TNF-α是IBD发病的主要促炎细胞因子之一。因为TNF水平存在于UC和CD患者的血清中。针对TNF-α的静脉和皮下生物制剂彻底改变了IBD的治疗方法。从而成为诱导和维持IBD缓解的最佳有效药物。在IBD患者中应用旨在中和TNF-α的抗体，在多达60％的患者中诱导令人满意的临床反应，并在大多数患者中引起疾病缓解的长期维持。有人提出，抗TNF-α药物通过直接中和使促炎细胞因子TNF-α失活，即，抑制炎症。然而,抗TNF-α抗体执行比简单的阻断更复杂的功能。
