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World J Gastroenterol. Sep 28, 2017; 23(36): 6628-6638
Published online Sep 28, 2017. doi: 10.3748/wjg.v23.i36.6628
Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology
Karen Dubois-Camacho, Payton A Ottum, Daniel Franco-Muñoz, Marjorie De la Fuente, Alejandro Torres-Riquelme, David Díaz-Jiménez, Mauricio Olivares-Morales, Gonzalo Astudillo, Rodrigo Quera, Marcela A Hermoso
Karen Dubois-Camacho, Daniel Franco-Muñoz, Marjorie De la Fuente, Alejandro Torres-Riquelme, David Díaz-Jiménez, Mauricio Olivares-Morales, Gonzalo Astudillo, Marcela A Hermoso, Innate Immunity Laboratory, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
Payton A Ottum, Neuroimmunology Laboratory, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
Marjorie De la Fuente, Division of Research, Clínica Las Condes, Santiago 7591046, Chile
Rodrigo Quera, Gastroenterology Department, Inflammatory Bowel Disease Program, Clínica Las Condes, Santiago 7591046, Chile
Author contributions: All authors equally contributed to literature review, critical revision and editing, and approval of the final version.
Supported by National Fund for Scientific and Technological Development No. 1170648 (MHR); Clínica Las Condes Academic Project PI2013-B002, UApoya No. 560959 (RQ); National Commission for Scientific and Technological Research scholarship No. 21150264 (DDJ), No. 21120682 (MOM); and MECESUP Scholarship No. UCH 0714 (KDC).
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Marcela A Hermoso, PhD, Full Professor, Innate Immunity Laboratory, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile. mhermoso@med.uchile.cl
Telephone: +56-2-29785672 Fax: +56-2-29786979
Received: February 25, 2017
Peer-review started: February 28, 2017
First decision: April 28, 2017
Revised: May 25, 2017
Accepted: July 4, 2017
Article in press: July 4, 2017
Published online: September 28, 2017
Abstract

Inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease, are chronic pathologies associated with a deregulated immune response in the intestinal mucosa, and they are triggered by environmental factors in genetically susceptible individuals. Exogenous glucocorticoids (GCs) are widely used as anti-inflammatory therapy in IBDs. In the past, patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission. However, this treatment often results in detrimental side effects. This downside drove the development of second generation GCs and more precise (non-systemic) drug-delivery methods. Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects. The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment. A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment. In this review, we examine the clinical characteristics of treatment with GCs, followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs. This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.

Keywords: Inflammatory bowel diseases, Ulcerative colitis, Crohn’s disease, Glucocorticoid dependence, Glucocorticoid resistance

Core tip: Glucocorticoids (GCs) are widely used in patients with Inflammatory Bowel Diseases who have moderate or severe disease activity; however, some of them do not respond to treatment or become dependent. Knowledge of both the clinical approach of GCs treatment as well as the molecular basis underlying their effects will help physicians prescribe drugs that will lead to better outcomes for patients.