Pathogenesis of Inflammatory Bowel Disease and Recent Advances in Biologic Therapies

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder with an unknown etiology. IBD is composed of two different disease entities: Crohn's disease (CD) and ulcerative colitis (UC). IBD has been thought to be idiopathic but has two main attributable causes that include genetic and environmental factors. The gastrointestinal tract in which this disease occurs is central to the immune system, and the innate and the adaptive immune systems are balanced in complex interactions with intestinal microbes under homeostatic conditions. However, in IBD, this homeostasis is disrupted and uncontrolled intestinal inflammation is perpetuated. Recently, the pathogenesis of IBD has become better understood owing to advances in genetic and immunologic technology. Moreover, new therapeutic strategies are now being implemented that accurately target the pathogenesis of IBD. Beyond conventional immunesuppressive therapy, the development of biological agents that target specific disease mechanisms has resulted in more frequent and deeper remission in IBD patients, with mucosal healing as a treatment goal of therapy. Future novel biologics should overcome the limitations of current therapies and ensure that individual patients can be treated with optimal drugs that are safe and precisely target IBD.

Keywords: Colitis; Crohn disease; Inflammatory bowel diseases; Physiopathology; Ulcerative.

Figure 1. Intestinal immune system. IL, interleukin; IFN, interferon; TNF, tumor necrosis factor; TGF, transforming growth factor; Th, helper T cell; Treg, regulatory T cell; TCR, T cell receptor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cell; TLR, toll-like receptor; NOD, nucleotide oligomerization domain.

Figure 2. Biologics regarding therapeutic targets (black: showed benefits; violet: no benefits). APC, antigen presenting cell; IEC, intestinal epithelial cell; TNF, tumor necrosis factor; MHC, major histocompatibility complex; TCR, T cell receptor; JAK, Janus kinase; TGF, transforming growth factor; IL, interleukin; MAdCAM, mucosal vascular addressing cell adhesion molecule.