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This article is part of the supplement: 25th European Workshop for Rheumatology Research

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Neutralizing IL-17 during re-activation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and IL-1

MI Koenders, E Lubberts, LAB Joosten and WB van den Berg

Author Affiliations

Department of Rheumatology, Experimental Rheumatology and Advanced Therapeutics, Radboud University Medical Center Nijmegen, The Netherlands

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Arthritis Research & Therapy 2005, 7(Suppl 1):P53  doi:10.1186/ar1574

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

Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd


Rheumatoid arthritis is characterized by an intermittent course of the disease with alternate periods of remission and relapse. T cells, and in particular the T-cell cytokine IL-17, are expected to be involved in this flare-up of arthritis.


To study the role of T-cell IL-17 in flare-up of experimental arthritis.


Antigen-induced arthritis was induced in C57Bl/6 mice by immunizing and boosting with mBSA/ complete Freund's adjuvant, and subsequent intra-articular injection of 60 μg mBSA. At week 4 of arthritis, 2 μg mBSA was injected into the arthritic joint to induce a flare-up of the smouldering inflammation. To study the role of IL-17 in this flare-up, neutralizing rabbit-anti-mouse-IL-17 antibodies (or control antibodies) were injected 2 hours prior to antigen rechallenge.


Quantitative PCR at various time points after arthritis induction showed that IL-17 mRNA expression was already upregulated at day 1, increased even more at day 2 and day 7, and clearly diminished at day 21. After antigen rechallenge, IL-17 mRNA expression rapidly increased, peaking at 4 hours with a 250-fold upregulation compared with naive mice.

Neutralizing IL-17 significantly prevented joint swelling, as measured by 99mTc uptake at day 1 (Fig. 1a). Arthritic knee joints were isolated at day 4, and histological analysis showed significantly suppressed joint inflammation (Fig. 1b) and cartilage proteoglycan depletion in the anti-IL-17-treated group.

thumbnailFigure 1. Joint swelling, (b) inflammation, and (c) bone erosion in arthritic mice before (background) and after flare-up of experimental arthritis, treated with anti-IL-17 antibodies or control antibodies. * P < 0.01, ** P < 0.005 versus control-treated group. R/L ratio, ratio between the mouse right inflamed knee joint (R) and left uninflamed knee joint (L).

Blocking IL-17 also clearly protected arthritic mice against bone erosions (Fig. 1c). Cathepsin K staining showed reduced osteoclast-like activity, and quantitative PCR showed reduced RANKL mRNA expression in the anti-IL-17-treated group. The degree of bone erosions strongly correlated with the severity of joint inflammation, suggesting that neutralizing IL-17 reduces bone erosion by suppressing joint inflammation.

Interestingly, mice treated with anti-IL-17 antibodies showed reduced protein levels of IL-1β, tumor necrosis factor alpha, and the cytokine-induced neutrophil chemoattractant KC, suggesting that IL-17 acts as an upstream mediator in destructive joint inflammation during flare-up of experimental arthritis.


These data indicate IL-17 to be an important upstream proinflammatory cytokine driving joint pathology during flare-up of experimental arthritis and suggest therapeutic benefit of neutralizing IL-17 during relapses of rheumatoid arthritis.