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Cytokines and joint erosion in arthritis

Nature Clinical Practice Rheumatology volume 4, pages 58–59 (2008)Cite this article

Bone erosion and cartilage destruction are hallmarks of rheumatoid arthritis (RA). Insight into how cytokines drive inflammatory and erosive processes has allowed the development of specific therapeutic tools to control synovitis and erosion, respectively. There is no doubt that inhibitors of tumor necrosis factor (TNF) are highly efficacious in the majority of RA cases, and the ATTRACT study indicates that treatment with the infliximab/methotrexate combination might retard bone erosion, even in patients who do not show a significant clinical response.1 Studies in animal models of arthritis have identified that cytokines such as TNF, but also interleukin (IL)-1 and T-cell-derived IL-17, are major drivers of osteoclastogenesis and subsequent osteoclast activation and bone damage through the induction of receptor activator of nuclear factor-κB ligand (RANKL). In addition to cytokine inhibition, the novel humanized antibody that neutralizes RANKL (denosumab) provides an attractive alternative to selectively inhibit inflammatory bone loss.

TNF alone is a major inflammatory cytokine; however, its direct destructive role seems limited. Marked synergy with IL-17 is noted, and it is now clear that TNF exerts much of its effects in joint destruction through induction of IL-1. This is elegantly demonstrated in transgenic mice that overexpress TNF, but completely lack IL-1:2 these mice still develop joint inflammation, with marked cellular infiltrates in the synovial tissue, but are fully protected from cartilage erosion and have much less bone damage than mice with intact IL-1. These findings fit with earlier observations from trials of IL-1 receptor antagonist (IL-1Ra) in patients with RA, where marked effects on erosion (∼40% retardation in radiological progression), and some influence on swelling and synovitis, were noted.3 It is currently unclear whether the higher efficacy of anti-TNF therapy, compared with IL-1Ra treatment, is due to increased involvement of TNF in patients with RA, or the poor pharmacokinetics of IL-1Ra.

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  1. 272, Rheumatology Research & Advanced Therapeutics, Radboud University, Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands w.vandenberg@reuma.umcn.nl

Authors and Affiliations

  1. WB van den Berg is Professor of Experimental Rheumatology and Head of the Laboratory of Rheumatology Research & Advanced Therapeutics at the Radboud University Nijmegen Medical Centre, The Netherlands.,

    Wim B van den Berg

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  1. Wim B van den Berg
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van den Berg, W. Cytokines and joint erosion in arthritis. Nat Rev Rheumatol 4, 58–59 (2008). https://doi.org/10.1038/ncprheum0683

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