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.

The S100B story: from biomarker to active factor in neural injury

“…Ulcerative colitis and Crohn's disease are the two major clinically defined forms of inflammatory bowel disease (for review, Nishida et al 2018). Although dysfunction of the mucosal immune system undoubtedly plays a role in the pathogenesis of inflammatory bowel disease (Kim and Cheon 2017), a role for the enteric nervous system (Goyal and Hirano 1996), located within the wall of the gastrointestinal tract, has been recognized in intestinal inflammation, also involving interactions with the intestinal microbiota (Margolis and Gershon 2016). Notably, enteric glial-derived S100B has been shown to be over-expressed, to correlate with the gut's inflammatory status and to stimulate NO production in human ulcerative colitis (Esposito et al 2007;Cirillo et al 2009).…”

Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings

“…Since gut microbiota controls the immunological homeostasis, 'dysbiosis' is therefore proven to induce and promote several gut-associated diseases primarily alongside diseases in other body parts of the human [67,88]. Inflammatory bowel disease (IBD) is one of the very common and debilitating problems of modern age humans characterized by the induction of inflammation and subsequent development of mucosal lesions [89,90]. The pathogenesis of IBD is mainly caused by the perturbation of normal gut microbial communities [1,91].…”

ZNF133 is associated with infliximab responsiveness in patients with inflammatory bowel diseases

“…IBD etiology has been associated with environmental, genetic, and immunoregulatory factors. Although IBD pathogenesis has not yet been completely clarified, it is thought that the production of various pro‐inflammatory cytokines, such as interleukin (IL)‐1β, IL‐6, IL‐23, and tumor necrosis factor‐α (TNF‐α), because of immunological imbalances between the host and microbes, is involved …”

“…Although IBD pathogenesis has not yet been completely clarified, it is thought that the production of various pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-23, and tumor necrosis factor-α (TNF-α), because of immunological imbalances between the host and microbes, is involved. 2 Tumor necrosis factor-α is one of the most potent inflammatory cytokines in IBD pathogenesis. It mediates multiple pro-inflammatory signals, neutrophil recruitment to inflammatory lesions, and induction of other pro-inflammatory cytokines.…”