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Cytokine networks—towards new therapies for rheumatoid arthritis

Nature Clinical Practice Rheumatology volume 1, pages 31–39 (2005)Cite this article

Abstract

Success achieved so far in the blockade of tumor necrosis factor and interleukin (IL)-1 in rheumatoid arthritis exemplifies the feasibility and potential therapeutic application of antagonizing cytokine signaling. Despite these advances, there remains a considerable unmet clinical need in this field. A number of preclinical development programs are ongoing to target a variety of cytokines that are central to immune regulation and tissue-matrix destruction in rheumatoid arthritis. Evidence indicates that IL-6 antagonists might represents a useful approach and preliminary data similarly identify IL-15 as an intriguing target. Numerous additional cytokines are under investigation at the preclinical stage, including IL-12–IL-23, IL-17 and IL-18. As therapeutic goals move from disease control towards remission induction, development of the capacity for cytokine targeting to modify the underlying immune dysregulation remains a major priority.

Key Points

  • Tumor necrosis factor blockade is effective in improving clinical signs and symptoms in rheumatoid arthritis (RA) patients and can ameliorate radiographic damage

  • Patient subsets that do not respond to tumor necrosis factor blockade, or respond only partially, represent an unmet clinical need

  • Numerous cytokine activities have now been described in RA synovia and studies in mouse arthritis models provide rational for their neutralization in clinical trials

  • Interleukin (IL)-6 and IL-15 are currently being tested in clinical studies in human RA

  • Preclinical evidence suggests that IL-12–IL-23, IL-18 and IL-17 might also offer therapeutic potential

  • Novel cytokine targets, including high mobility group box 1 protein and adipokines, might offer future therapeutic utility

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Figure 1: Cytokines regulate various processes necessary for development of inflammatory synovitis in rheumatoid arthritis.
Figure 2: Cytokines mediate feedback between cells of the immune cells and host tissue cells.
Figure 3: Cytokine signaling in the synovial membrane.

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Acknowledgements

The authors acknowledge funding support from the Arthritis Research Campaign and The Wellcome Trust (UK).

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Authors and Affiliations

  1. Professor of Experimental Medicine and an Honorary Consultant Rheumatologist at the Centre for Rheumatic Diseases,

    Iain B McInnes & Foo Y Liew

  2. Gardiner Professor of Immunology and the Head of the Division of Immunology, Infection and Inflammation, University of Glasgow, UK

    Iain B McInnes & Foo Y Liew

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Correspondence to Iain B McInnes.

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McInnes, I., Liew, F. Cytokine networks—towards new therapies for rheumatoid arthritis. Nat Rev Rheumatol 1, 31–39 (2005). https://doi.org/10.1038/ncprheum0020

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