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  • Review Article
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Immune resolution mechanisms in inflammatory arthritis

Nature Reviews Rheumatology volume 13, pages 87–99 (2017)Cite this article

Subjects

Key Points

  • Acute inflammation resolves actively through the engagement of specific proresolving mediators and mechanisms

  • The effect of failed resolution in chronic inflammatory settings is markedly unappreciated

  • Novel technologies afford analytical definition of proresolving mediators in clinical samples, providing new opportunities for stratification and target identification

  • Therapeutic strategies based on the biology of resolution can guide the development of novel medicines for the clinical management of inflammatory arthritis

  • Resolution-based therapies might be less burdened by unwanted effects than existing therapies and would activate tissue-protective mechanisms within patients

Abstract

The past two decades have witnessed major advancements in the clinical management of inflammatory arthritis, with new treatment strategies in some cases providing a marked improvement in patient outcomes. However, it is widely accepted that current strategies do not provide the 'total therapeutic solution', in view of the proportion of patients who do not respond to therapy, the important incidence of adverse effects and the development of an immune response against antibodies or fusion proteins used therapeutically. Moreover, although some therapeutic approaches can effectively bring about an end to inflammation, mechanisms to promote the recovery and/or repair of damage are required. Harnessing the concepts and mechanisms of the resolution of inflammation is a new approach to the treatment of inflammatory pathologies; this approach could help address the unmet need for new therapeutic approaches that not only control but also revert the course of inflammatory rheumatic diseases.

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Figure 1: Dynamics of the inflammatory response.
Figure 2: Biosynthetic pathways leading to the production of specialized proresolving lipid mediators.

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Acknowledgements

The authors received funding support from the Wellcome Trust Programme (grant 086867/Z/08/Z to M.P.), the UK Medical Research Council (grant MR/K013068/1 to M.P.) and Arthritis Research UK (Career Progression Fellowship 20387 to D.C. and Career Development Fellowship 19909 to L.V.N.). J. D. received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 677542). J.D. is also supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant 107613/Z/15/Z). This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institutes of Health Research.

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  1. The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Mauro Perretti, Dianne Cooper, Jesmond Dalli & Lucy V. Norling

  2. QMUL Lipid Mediator Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Jesmond Dalli

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M.P. researched data for article. All authors made a substantial contribution to discussion of content and writing the article. D.C., J.D. and L.V.N. reviewed/edited the manuscript before submission.

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Correspondence to Mauro Perretti.

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M.P. is an adviser to Palatin Technologies and a member of the Scientific Advisory Board of Antibe Therapeutics. The other authors declare they have no competing interests.

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Perretti, M., Cooper, D., Dalli, J. et al. Immune resolution mechanisms in inflammatory arthritis. Nat Rev Rheumatol 13, 87–99 (2017). https://doi.org/10.1038/nrrheum.2016.193

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