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  • Review Article
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Systemic effects of IL-17 in inflammatory arthritis

Nature Reviews Rheumatology volume 15, pages 491–501 (2019)Cite this article

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Abstract

Inflammatory arthritis occurs in many diseases and is characterized by joint inflammation and damage. However, the inflammatory state in arthritis is commonly associated with systemic manifestations, which are generally linked to a poor prognosis. The pro-inflammatory cytokine IL-17 functions within a complex network of cytokines and contributes to the pathogenesis of various inflammatory diseases. Three IL-17 inhibitors have already been approved for the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. After a brief description of IL-17 and its local effects on joints, this Review focuses on the systemic effects of IL-17 in inflammatory arthritis. Increased circulating concentrations of bioactive IL-17 mediate changes in blood vessels, liver and cardiac and skeletal muscles. The effects of IL-17 on vascular and cardiac cells might contribute to the increased risk of cardiovascular events that occurs in all patients with inflammatory disorders. In the liver, IL-17 contributes to the high circulating concentrations of acute-phase proteins, such as C-reactive protein, and the appearance of liver lesions. In skeletal muscle, IL-17 contributes to muscle contractibility defects and weakness. Thus, targeting IL-17 might have beneficial effects at both local and systemic levels, and could also be proposed for the treatment of a wider range of inflammatory diseases.

Key points

  • Inflammatory arthritis is associated with systemic comorbidities that lead to a poor prognosis.

  • Alone, or in cooperation with other cytokines, IL-17 participates in the establishment and chronicity of several inflammatory diseases, including inflammatory arthritis.

  • IL-17 can mediate pleiotropic effects throughout the body as IL-17 receptors are expressed on most cell types.

  • IL-17 contributes to the increased risk of cardiovascular events common to inflammatory diseases by affecting vascular and cardiac cells.

  • IL-17 induces increased concentrations of C-reactive protein and contributes to liver changes by inducing an inflammatory response in liver cells.

  • The systemic effects of IL-17 suggest that targeting this cytokine might be beneficial for the treatment of arthritic and non-arthritic conditions, in addition to inflammatory arthritis.

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Fig. 1: Main biological functions of IL-17.
Fig. 2: Effects of IL-17 on cells of the blood vessels, liver, heart and skeletal muscle.
Fig. 3: Systemic effects of IL-17.

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Acknowledgements

The work of A.B. is supported by the Ministry of Education and Research, France. P.M. is a senior member of the Institut Universitaire de France. His laboratory is supported in part by the IHU OPERA.

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Nature Reviews Rheumatology thanks S. Divanovic, P. Wenzel and E. Lubberts for their contribution to the peer review of this work.

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  1. Immunogenomics and Inflammation Research Unit, EA 4130, University of Lyon, Hospices Civils de Lyon, Lyon, France

    Audrey Beringer & Pierre Miossec

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  1. Audrey Beringer
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A.B. researched data for the article. P.M. reviewed and/or edited the manuscript before submission. Both authors made a substantial contribution to discussion of content and wrote the article.

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Correspondence to Pierre Miossec.

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P.M. holds a patent on the IL-17 bioassay (patent number 20170176456). A.B. declares no competing interests.

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Beringer, A., Miossec, P. Systemic effects of IL-17 in inflammatory arthritis. Nat Rev Rheumatol 15, 491–501 (2019). https://doi.org/10.1038/s41584-019-0243-5

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