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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)

Poster presentation

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: http://arthritis-research.com/content/14/S1/P62


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 (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

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.

Results

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)

Conclusion

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.