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New targets
Interleukin 6 receptor as a target for the treatment of rheumatoid arthritis
  1. E Choy
  1. Academic Department of Rheumatology, GKT School of Medicine, King’s College Hospital, London, UK
  1. Correspondence to:
    Dr E Choy, Academic Department of Rheumatology, 2nd Floor, Weston Education Centre, King’s College London, Cutcombe Road, London SE5 9PJ, UK;
    ernest.choy{at}kcl.ac.uk

https://doi.org/10.1136/ard.62.suppl_2.ii68

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    Chronic synovial inflammation and joint damage are cardinal features of rheumatoid arthritis (RA). Although the precise cause remains unknown, cytokines have a major pathogenic role. The therapeutic benefit of antagonists of tumour necrosis factor alpha (TNFα) and interleukin (IL) 1 in RA provide the best evidence for the importance of cytokines in mediating synovitis. Although IL1 and TNFα blocking treatments are effective, some patients have refractory disease and fail to respond. The reasons for this are yet to be elucidated. In other patients, treatment has had to be withdrawn because of side effects. When anticytokine treatments are withdrawn, in most cases, it is necessary to substitute other disease modifying antirheumatic drugs (DMARDs) because of resurgence in disease activity. Many patients fail to respond to multiple DMARDs, and alternative treatments are needed. As targeting monokines has produced effective treatment of RA, other cytokines have become attractive therapeutic targets. One of these is IL6.

    IL6

    IL6 is a 26 kDa pleiotropic cytokine. It was known initially as B cell stimulatory factor 2 because it stimulates B cell growth and maturation. Likewise it is also known as hepatocyte stimulating factor because it activates hepatocytes to produce acute phase reactants such as C reactive protein and amyloid A. IL6 is produced by a wide range of cell types including lymphocytes, monocytes, fibroblasts,1 synoviocytes,2 and endothelial cells.3 Structurally, it shares homology with other cytokines: oncostatin M, IL11, leukaemia inhibitory factor, ciliary neurotrophic factor, and cardiotrophin 1. Together, these cytokines constitute the IL6 superfamily. In addition to structural homology, these cytokines use a common signal transduction pathway to stimulate cellular activation. All of the cytokines in the IL6 …

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