Role of proinflammatory cytokines in the pathophysiology of osteoarthritis

Abstract

Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.

Key Points

  • Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and synovial membrane inflammation

  • Proinflammatory cytokines are critical mediators in the disturbed metabolism and enhanced catabolism of tissue in the OA joint

  • Interleukin (IL)-1β, tumor necrosis factor (TNF) and IL-6 seem to be the main proinflammatory cytokines involved in the pathophysiology of OA

  • Data from cellular and animal studies have provided substantial evidence that blocking IL-1β and TNF production could counteract the degradative mechanisms associated with OA pathology

  • Anticytokine therapies in OA clinical trials have so far yielded variable results

  • A better understanding of the individual roles and functions of cytokines, such as IL-1β, TNF and IL-6, is of the utmost importance in order to develop adequate and specific anticytokine therapies

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Figure 1: The role of proinflammatory cytokines in the pathophysiology of OA.

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Acknowledgements

The authors would like to thank Francois Mineau for his work on the figure for this review article.

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All authors contributed equally to researching data for the article, providing a substantial contribution to discussions of the content, writing the article, and to the review and/or editing of the manuscript before submission.

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Correspondence to Johanne Martel-Pelletier.

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Kapoor, M., Martel-Pelletier, J., Lajeunesse, D. et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7, 33–42 (2011). https://doi.org/10.1038/nrrheum.2010.196

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