Review Article | Published:

Cytokines in inflammatory bowel disease

Nature Reviews Immunology volume 14, pages 329342 (2014) | Download Citation


Cytokines have a crucial role in the pathogenesis of inflammatory bowel diseases (IBDs), such as Crohn's disease and ulcerative colitis, where they control multiple aspects of the inflammatory response. In particular, the imbalance between pro-inflammatory and anti-inflammatory cytokines that occurs in IBD impedes the resolution of inflammation and instead leads to disease perpetuation and tissue destruction. Recent studies suggest the existence of a network of regulatory cytokines that has important implications for disease progression. In this Review, we discuss the role of cytokines produced by innate and adaptive immune cells, as well as their relevance to the future therapy of IBD.

Key points

  • Genome-wide association studies have identified several inflammatory bowel disease (IBD) susceptibility loci that contain genes that encode cytokines and proteins involved in cytokine signalling. In particular, recent work has found that loss-of-function mutations in the genes encoding interleukin-10 (IL-10) and the IL-10 receptor are associated with very early-onset IBD.

  • Cytokines not only drive intestinal inflammation and diarrhoea in IBD but may also regulate extra-intestinal disease manifestations (for example, arthralgia or arthritis) and systemic effects. Furthermore, cytokines seem to have a crucial role in driving complications of IBD such as intestinal stenosis, fistula formation and colitis-associated neoplasias.

  • Studies using tissue from patients with IBD and animal models of IBD have identified cytokines as potential new targets for the therapy of intestinal inflammation. Relevant targets include pro-inflammatory cytokines, such as IL-6, IL-12, IL-23 and IL-21, as well as anti-inflammatory cytokines, such as IL-10 and transforming growth factor-β.

  • Anti-cytokine therapies involving tumour necrosis factor (TNF)-specific agents form an important cornerstone of clinical therapy in both Crohn's disease and ulcerative colitis. TNF-specific antibodies suppress chronic intestinal inflammation and may induce mucosal healing in IBD.

  • Several new anti-cytokine agents have shown little or no efficacy in IBD, suggesting the existence of a highly regulated cytokine network. New approaches for anti-cytokine therapies may include multi-cytokine blockers, such as tofacitinib.

  • New cytokine targets, optimized delivery systems for anti-cytokine agents and personalized medicine may pave the way towards more effective clinical approaches by targeting the expression or function of pro-inflammatory and anti-inflammatory cytokines in patients with IBD.

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The research of M.F.N. is supported by the Clinical Research Group (CEDER) of the German Research Council (DFG), the DFG Collaborative Research Centers 643 and 796, The German Cancer Aid organization, the United European Gastroenterology Research Prize, the DFG Graduate School of Excellence School in Advanced Optical Technologies, the Excellence program of the Friedrich-Alexander-Universität Erlangen-Nürnberg (Ludwig Demling Center), Germany, and the Interdisciplinary Center for Clinical Research (IZKF) and ELAN (Fonds für Forschung und Lehre) programmes of the University Erlangen-Nürnberg, Germany.

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  1. Department of Medicine 1, University of Erlangen-Nürnberg, Kussmaul Campus for Medical Research, 91054 Erlangen, Germany.

    • Markus F. Neurath


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Competing interests

M.F.N. has served as an adviser for MSD Pharmaceuticals, AbbVie, Pentax Corporation and Giuliani Pharma.

Corresponding author

Correspondence to Markus F. Neurath.


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