Back to Browse Journals » Biologics: Targets and Therapy » Volume 3

Biologic targeting in the treatment of inflammatory bowel diseases

Authors Matteo Bosani, Sandro Ardizzone, Gabriele Bianchi Porro

Published Date February 2009 Volume 2009:3 Pages 77—97

DOI http://dx.doi.org/10.2147/BTT.S3080

Published 9 February 2009

Matteo Bosani, Sandro Ardizzone, Gabriele Bianchi Porro

Chair of Gastroenterology, “L. Sacco” University Hospital, Milan, Italy

Abstract: The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Under normal situations, the intestinal mucosa is in a state of “controlled” inflammation regulated by a delicate balance of proinflammatory (tumor necrosis factor [TNF-α], interferon-gamma [IFN-γ], interleukin-1 [IL-1], IL-6, IL-12 and anti-inflammatory cytokines IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may therefore be a logical target for inflammatory bowel disease therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-κB), and other miscellaneous therapies are being evaluated as potential therapies for the treatment of inflammatory bowel disease. In this context, infliximab and adalimumab are currently the only biologic agents approved in Europe for the treatment of inflammatory Crohn’s disease. Other anti-TNF biologic agents have emerged, including CDP571, certolizumab pegol, etanercept, onercept. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanism involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn’s disease. Therapeutics agents to inhibit leukocyte trafficking include natalizumab (approved for use in Crohn’s disease in USA), MLN-02, and ISIS 2302. Other agents being investigated for the treatment of Crohn’s disease include inhibitors of T cell activation, proinflammatory cytokine receptors, Th1 polarization, growth hormone, and growth factors. Agents being investigated for treatment of ulcerative colitis include many of those mentioned above. Controlled clinical trials are currently being conducted, exploring the safety and efficacy of old and new biologic agents, and the search certainly will open new and exciting perspective on the development of therapies for inflammatory bowel disease. A review is made of the main areas of research exploring the mechanisms associated with the pathogenesis of IBD, providing advances in the agents currently in use, and identifying a host of new therapeutic biologic targets.

Keywords: Crohn’s disease, ulcerative colitis, biological therapy

This paper has been retracted.

Download Article [PDF] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Nanostructured polyurethane-poly-lactic- co-glycolic acid scaffolds increase bladder tissue regeneration: an in vivo study

Yao C, Hedrick M, Pareek G, Renzulli J, Haleblian G, Webster TJ

International Journal of Nanomedicine 2013, 8:3285-3296

Published Date: 28 August 2013

Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer

Chauhan A, Zubair S, Tufail S, Sherwani A, Sajid M, Raman SC, Azam A, Owais M

International Journal of Nanomedicine 2011, 6:2305-2319

Published Date: 12 October 2011

A case of cephalothin-associated urolithiasis

Ivan WM Lim, Peter JO Stride, Robert L Horvath

Clinical Pharmacology: Advances and Applications 2011, 3:1-3

Published Date: 28 February 2011

Chronomodulated press-coated pulsatile therapeutic system for aceclofenac: optimization of factors influencing drug release and lag time

Sumit Patil, Swati Pund, Amita Joshi, et al

ChronoPhysiology and Therapy 2011, 1:1-10

Published Date: 21 February 2011

Amino acid-responsive Crohn's disease: a case study

Alvin Stein, Marty Hinz, Thomas Uncini

Clinical and Experimental Gastroenterology 2010, 3:171-177

Published Date: 6 December 2010

Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

Eduardo Pimenta, Suzanne Oparil

Vascular Health and Risk Management 2009, 5:453-463

Published Date: 19 May 2009