IBD Center, Division of Gastroenterology, IRCCS Istituto Clinico Humanitas ICH 20089, Rozzano, Milan, Italy.
Curr Drug Targets. 2013 Nov;14(12):1508-21. doi: 10.2174/13894501113146660224.
Inflammatory bowel diseases (IBD) are chronic, relapsing, and destructive inflammatory disorders of the gastrointestinal tract. Both Crohn's disease (CD) and ulcerative colitis (UC) seem to arise from an impaired dialog between the environment and gut microbiota in genetically susceptible hosts, leading to an inappropriate immune activation and resulting in the over-production of pro-inflammatory cytokines. IL-6 is a key modulator of inflammatory response. It is a phylogenetically important cytokine with relevance in IBD, as well as in other chronic inflammatory diseases and cancer. Influencing the production of this cytokine can change the balance of effector CD4+ T cell subsets and induce B cell antibody production. Moreover, given IL-6 is mostly produced from innate immune cells such as macrophages, neutrophils and mast cells, it is a strategic bridge between the innate and the adaptive system. Interestingly, IL-6 induced signaling can be primarily seen in a relatively small number of IL-6 responsive cells whereas in a chronic phase of inflammation it is able to activate almost all cells of the body through a process known as trans-signaling. In this review, we discuss the role of IL-6 in chronic inflammation, with particular emphasis on its role in CD and UC, and we explore the potential to develop anti-IL-6 agents for IBD treatment.
炎症性肠病（IBD）是一种慢性、复发性和破坏性的胃肠道炎症性疾病。克罗恩病（CD）和溃疡性结肠炎（UC）似乎都源于遗传易感宿主中环境与肠道微生物群之间受损的对话，导致免疫激活不当，从而导致促炎细胞因子的过度产生。IL-6 是炎症反应的关键调节因子。它是一种在 IBD 以及其他慢性炎症性疾病和癌症中具有相关性的具有重要进化意义的细胞因子。影响这种细胞因子的产生可以改变效应性 CD4+T 细胞亚群的平衡，并诱导 B 细胞产生抗体。此外，由于 IL-6 主要由先天免疫细胞（如巨噬细胞、中性粒细胞和肥大细胞）产生，因此它是先天免疫系统和适应性免疫系统之间的战略桥梁。有趣的是，IL-6 诱导的信号可以主要在相对较少的 IL-6 反应细胞中看到，而在炎症的慢性阶段，它可以通过一种称为转信号的过程激活几乎所有的身体细胞。在这篇综述中，我们讨论了 IL-6 在慢性炎症中的作用，特别强调了它在 CD 和 UC 中的作用，并探讨了开发用于治疗 IBD 的抗 IL-6 药物的潜力。
