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Fibrostenotic Inflammatory Bowel Disease pp 59–75Cite as

Cytokine and Anti-Cytokine Agents as Future Therapeutics for Fibrostenosing IBD

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Abstract

The pathogenesis of stricture formation in inflammatory bowel disease is a complex process with a wide variety of clinical, genetic, epigenetic, and environmental risk factors. Originally thought to be a consequence of chronic inflammation, new evidence arises for non-inflammatory contributors to stricture formation, suggesting an intricate interplay of cellular, molecular, and additional host/environmental factors. Although no specific medical treatments for fibrostenotic intestinal strictures currently exist, understanding the molecular pathways involved in stricture formation will undoubtedly guide therapeutic developments. As mediators of inflammation and immunoregulation, cytokines are key effectors in the fibrotic process. Accordingly, targeting inflammation, in part via cytokine blockade, has been the mainstay of therapy in IBD. In many cases, inflammatory disease is associated with significant fibrotic change, as increased inflammation perpetuates the cascade of mucosal repair. Thus, inflammatory cytokine-targeted therapy may serve as one potential avenue for treating fibrostenosis. As regulatory and repair mechanisms have been implicated in fibrosis as well, either as sequelae of inflammation or via de novo pathways, a parallel route for treating intestinal fibrosis may be the targeting of “regulatory” cytokines. This chapter will highlight the relevant contributions and potential therapeutic targeting of cytokines involved in inflammatory and regulatory pathways leading to fibrosis.

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Acknowledgement

This work is supported NIH T32 DK07180-43 (NJ), Specialty Training and Advanced Research (STAR) Program at UCLA (NJ), NIH R01 DK056328-16 (NJ, SRT and DQS), NIH K08 Career Development Award DK093578 (DQS), and the F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute (NJ, SRT and DQS).

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The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Noam Jacob, Stephan R. Targan & David Q. Shih

  2. Vatche and Tamar Manoukian, Division of Digestive Diseases, Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Noam Jacob

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  1. Noam Jacob
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  2. Stephan R. Targan
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Correspondence to David Q. Shih .

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  1. Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Florian Rieder

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Jacob, N., Targan, S.R., Shih, D.Q. (2018). Cytokine and Anti-Cytokine Agents as Future Therapeutics for Fibrostenosing IBD. In: Rieder, F. (eds) Fibrostenotic Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-90578-5_5

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