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  • Review Article
  • Published:

Persisting eicosanoid pathways in rheumatic diseases

Nature Reviews Rheumatology volume 10, pages 229–241 (2014)Cite this article

Subjects

Key Points

  • Eicosanoid pathways have a major role in the pathogenesis of rheumatic diseases, including rheumatoid arthritis, osteoarthritis, idiopathic inflammatory myositis, systemic lupus erythematosus and gouty arthritis

  • Despite potent suppression of specific inflammatory mechanisms by a wide range of antirheumatic drugs, the cyclooxygenase and 5-lipoxygenase pathways remain overexpressed and can contribute to subclinical inflammation and relapse of rheumatic disease

  • Several enzymes of the arachidonic acid cascade (part of the eicosanoid pathway) and eicosanoid receptors are well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases

  • The combination of microsomal prostaglandin E synthase 1 inhibition with current antirheumatic treatments or with leukotriene inhibitors might improve the effect of anti-inflammatory agents in certain disorders

Abstract

An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.

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Figure 1: Biosynthesis of eicosanoids.
Figure 2: Current and putative targets in arachidonic acid cascade for anti-inflammatory treatment in rheumatic diseases.

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Acknowledgements

P.-J.J and M.K. would like to acknowledge support by The Swedish Research Council, The Swedish Rheumatism Association, King Gustaf V 80 years Foundation, The Swedish Society of Medicine, Karolinska Institutet Foundation, The Swedish County Council and Marianne and Marcus Wallenberg foundation.

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  1. Department of Medicine, Rheumatology Unit, D2:01, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, SE-17176, Sweden

    Marina Korotkova & Per-Johan Jakobsson

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  1. Marina Korotkova
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M.K. researched data for the article. Both authors contributed equally to discussion of content, writing, and reviewing/editing the manuscript before submission.

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Correspondence to Per-Johan Jakobsson.

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P.-J.J. is a member of the board of directors for NovaSAID AB. M.K. declares no competing interests.

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Supplementary Table 1

A list of the described eicosanoids and their receptors (DOC 54 kb)

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Korotkova, M., Jakobsson, PJ. Persisting eicosanoid pathways in rheumatic diseases. Nat Rev Rheumatol 10, 229–241 (2014). https://doi.org/10.1038/nrrheum.2014.1

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