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Cytokines in rheumatoid arthritis — shaping the immunological landscape

Nature Reviews Rheumatology volume 12, pages 63–68 (2016)Cite this article

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Abstract

Cytokine-mediated pathways are central to the pathogenesis of rheumatoid arthritis (RA). The purpose of this short Opinion article is to briefly overview the roles of cytokine families in the various phases and tissue compartments of this disease. In particular, we consider the combinatorial role played by cytokines in mediating the overlapping innate and adaptive immune responses associated with disease onset and persistence, and also those cytokine pathways that, in turn, drive the stromal response that is critical for tissue localization and associated articular damage. The success of cytokine inhibition in the clinic is also considerable, not only in offering remarkable therapeutic advances, but also in defining the hierarchical position of distinct cytokines in RA pathogenesis, especially IL-6 and TNF. This hierarchy, in turn, promises to lead to the description of meaningful clinical endotypes and the consequent possibility of therapeutic stratification in future.

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Figure 1: Cytokine profiles that subserve the biology of discrete phases of the rheumatoid arthritis disease process.
Figure 2: Functional modules exist within complex cytokine networks.

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Acknowledgements

The authors receive funding support from Arthritis Research UK via the Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence.

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Author notes

  1. Iain B. McInnes, Christopher D. Buckley and John D. Isaacs: All authors are affiliated with the Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence.

Authors and Affiliations

  1. Institute of Infection, Immunity & Inflammation, University of Glasgow, 120 University Place, Glasgow, G12 8QQ, UK

    Iain B. McInnes

  2. Rheumatology Research Group, Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, Edgbaston, B15 2WB, Birmingham, UK

    Christopher D. Buckley

  3. NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, UK

    John D. Isaacs

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All authors researched data for article, made substantial contributions to discussions of the content, wrote the article and reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Iain B. McInnes.

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Competing interests

I.B.M. declares that he has received research funding and honouraria from AbbVie, BMS, MSD, Pfizer, Roche and UCB, all of whom make biologic agents used in the treatment of rheumatoid arthritis. C.D.B. declares that he has received honouraria and research funding from Novartis, Pfizer, Roche and UCB. J.D.I. declares that he has received research funding and honouraria from AbbVie, BMS, Novartis, Janssen, Pfizer and Roche.

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McInnes, I., Buckley, C. & Isaacs, J. Cytokines in rheumatoid arthritis — shaping the immunological landscape. Nat Rev Rheumatol 12, 63–68 (2016). https://doi.org/10.1038/nrrheum.2015.171

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