Pathogenesis of Inflammatory Bowel Disease and Recent Advances in Biologic Therapies

Overview

Journal Immune Netw

Specialty Allergy & Immunology

Date 2017 Mar 7

PMID 28261018

Citations 132

Authors

Duk Hwan Kim

Jae Hee Cheon

Affiliations

Soon will be listed here.

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.

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References

Shen J, Zuo Z, Mao A . Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled trials. Inflamm Bowel Dis. 2013; 20(1):21-35. DOI: 10.1097/01.MIB.0000437495.30052.be. View

Caruso R, Fina D, Peluso I, Stolfi C, Fantini M, Gioia V . A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells. Gastroenterology. 2007; 132(1):166-75. DOI: 10.1053/j.gastro.2006.09.053. View

Steinbach E, Plevy S . The role of macrophages and dendritic cells in the initiation of inflammation in IBD. Inflamm Bowel Dis. 2013; 20(1):166-75. PMC: 4098861. DOI: 10.1097/MIB.0b013e3182a69dca. View

van der Sluis M, de Koning B, de Bruijn A, Velcich A, Meijerink J, van Goudoever J . Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology. 2006; 131(1):117-29. DOI: 10.1053/j.gastro.2006.04.020. View

Ghoreschi K, Laurence A, OShea J . Janus kinases in immune cell signaling. Immunol Rev. 2009; 228(1):273-87. PMC: 2782696. DOI: 10.1111/j.1600-065X.2008.00754.x. View

Hanauer S, Feagan B, Lichtenstein G, Mayer L, Schreiber S, Colombel J . Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002; 359(9317):1541-9. DOI: 10.1016/S0140-6736(02)08512-4. View

Erdman S, Rao V, Poutahidis T, Ihrig M, Ge Z, Feng Y . CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res. 2003; 63(18):6042-50. View

Monteleone I, Pallone F, Monteleone G . Th17-related cytokines: new players in the control of chronic intestinal inflammation. BMC Med. 2011; 9:122. PMC: 3239315. DOI: 10.1186/1741-7015-9-122. View

Willing B, Halfvarson J, Dicksved J, Rosenquist M, Jarnerot G, Engstrand L . Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm Bowel Dis. 2008; 15(5):653-60. DOI: 10.1002/ibd.20783. View

10.

Papadakis K, Targan S . Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med. 2000; 51:289-98. DOI: 10.1146/annurev.med.51.1.289. View

11.

Maas R, Muller-Hansma A, Esselink R, Murk J, Warnke C, Killestein J . Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases. J Neurol. 2016; 263(10):2004-21. PMC: 5037162. DOI: 10.1007/s00415-016-8217-x. View

12.

Lennard L . The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol. 1992; 43(4):329-39. DOI: 10.1007/BF02220605. View

13.

Dewit O, Moreels T, Baert F, Peeters H, Reenaers C, De Vos M . Limitations of extensive TPMT genotyping in the management of azathioprine-induced myelosuppression in IBD patients. Clin Biochem. 2011; 44(13):1062-1066. DOI: 10.1016/j.clinbiochem.2011.06.079. View

14.

Reinisch W, de Villiers W, Bene L, Simon L, Racz I, Katz S . Fontolizumab in moderate to severe Crohn's disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. Inflamm Bowel Dis. 2009; 16(2):233-42. DOI: 10.1002/ibd.21038. View

15.

Sandborn W, Colombel J, Sands B, Rutgeerts P, Targan S, Panaccione R . Abatacept for Crohn's disease and ulcerative colitis. Gastroenterology. 2012; 143(1):62-69.e4. DOI: 10.1053/j.gastro.2012.04.010. View

16.

Uhlig H, McKenzie B, Hue S, Thompson C, Joyce-Shaikh B, Stepankova R . Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity. 2006; 25(2):309-18. DOI: 10.1016/j.immuni.2006.05.017. View

17.

Huang Y, Chen Z . Inflammatory bowel disease related innate immunity and adaptive immunity. Am J Transl Res. 2016; 8(6):2490-7. PMC: 4931145. View

18.

Stremmel W, Merle U, Zahn A, Autschbach F, Hinz U, Ehehalt R . Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis. Gut. 2005; 54(7):966-71. PMC: 1774598. DOI: 10.1136/gut.2004.052316. View

19.

Iliev I, Funari V, Taylor K, Nguyen Q, Reyes C, Strom S . Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012; 336(6086):1314-7. PMC: 3432565. DOI: 10.1126/science.1221789. View

20.

Hueber W, Sands B, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins P . Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012; 61(12):1693-700. PMC: 4902107. DOI: 10.1136/gutjnl-2011-301668. View