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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

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Two cases of multiple-drug-resistant adult-onset Still's disease treated successfully with tocilizumab - the relationship between interleukin 6 and 18

Kojiro Sato*, Akinori Yamamoto, Yoshihiro Yoshida and Toshihide Mimura

  • * Corresponding author: Kojiro Sato

Author Affiliations

Department of Rheumatology and Applied Immunology, Saitama Medical University, Saitama 350-0495, Japan

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Arthritis Research & Therapy 2012, 14(Suppl 1):P62  doi:10.1186/ar3663

The electronic version of this article is the complete one and can be found online at:

Published:9 February 2012

© 2012 Sato et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Adult-onset Still's disease (AOSD) is an inflammatory disease of unknown cause characterized by a high spiking fever, arthritis and evanescent rash. The mainstay of treatment is glucocorticoids with or without immunosuppressants. Recently, biologics such as anti-tumor necrosis factor (TNF) antibodies have also been tried in certain refractory cases.


We have had two cases of AOSD which were treated successfully with anti-interleukin (IL-) 6-receptor antibody, tocilizumab (TOC). (Case 1) A 36-year-old woman who was diagnosed 8 years previously, and had been treated with various DMARDs plus etanercept (ETA) or adalimumab, presented with a high spiky fever and elevated liver enzymes. After excluding infection, she was treated with TOC. (Case 2) A 26-year-old man with new-onset AOSD, which was shown to be resistant to multiple immunosuppressants including infliximab and ETA, was treated with TOC starting 7 months after the diagnosis. In both cases, serum IL-18 was extremely high, and TOC promptly improved clinical symptoms and liver function. The high level of serum ferritin also became normalized. Interestingly, especially in case 2, the level of IL-18 remained high after the administration of TOC, suggesting that IL-18 is located either upstream of, or at the same level as, IL-6 in the pathogenesis of AOSD. Next, we cultured human monocytes derived from healthy controls with or without the presence of IL-6 and/or IL-18 in vitro. The level of ferritin in the supernatant was significantly increased only when both IL-6 and IL-18 were added, indicating that IL-6 and IL-18 have a synergistic effect on the production of ferritin (Figure 1).

thumbnailFigure 1. The level of ferritin in the supernatant of monocytes cultured with or without the presence of IL-6 and/or IL-18 (10 ng/mL each)


TOC can be a first-line biologic applicable against multiple-drug-resistant AOSD. If an IL-18 blocker is developed, however, it may be even more beneficial in that it may block the cascade of inflammation at a point further upstream.