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

  • Noam Jacob
  • Stephan R. Targan
  • David Q. Shih
Chapter

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.

Keywords

Inflammatory bowel disease Strictures Crohn’s disease Ulcerative colitis Fibrostenosis 

Notes

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).

Conflict of Interest

The authors have declared that no conflict of interest exists.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Noam Jacob
    • 1
    • 2
  • Stephan R. Targan
    • 1
  • David Q. Shih
    • 1
  1. 1.F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical CenterLos AngelesUSA
  2. 2.Vatche and Tamar Manoukian, Division of Digestive Diseases, Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA

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