Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Recognition of IL-23 Dependent and Independent Stages during Autoimmune Collagen-Induced Arthritis.

Cornelissen2,  Ferry, Asmawidjaja2,  Patrick, Mus2,  Anne-Marie, Corneth2,  Odilia, Kikly1,  Kristine, Lubberts2,  Erik

Eli Lilly
Erasmus MC, University Medical Center


IL-23 is a heterodimeric cytokine composed of an IL-12/23-p40 subunit together with an IL-287-specific p19 subunit. The critical role of IL-23 in the development of autoimmune collagen-induced arthritis (CIA) has been shown using IL-23p19 knockout mice. However, it is unknown what the role of IL-23 is at later stages of CIA and during T cell memory mediated flare-up arthritis.

Materials and Methods:

In one set of experiments, an anti-IL-23p19-specific antibody (anti-IL-23) was injected starting 15 days after the first immunization with type II collagen (CII) but before the booster injection of CIA. In another set of experiments, anti-IL-23 was injected starting after the first signs of CIA. Splenocytes, popliteal lymph-node cells (PLNs) and cells isolated from ankles were assessed for intracellular cytokine production by flow cytometry. Serum IgG and IL-6 levels were measured. To test the role of anti-IL-23 in a memory T cell driven arthritis model we utilized the flare-up induced mBSA arthritis model.


Neutralizing IL-23 starting 15 days after the first CII-immunization significantly delayed and suppressed the onset of CIA. In these anti-IL-23 treated mice, serum IL-6 was lower compared to control mice. In addition, the mean fluorescent intensity (MFI) of splenic CD4+ TNF expressing cells was significantly lower in the anti-IL-23p19 treated group compared to the isotype control group. In the sera of anti-IL-23 treated mice, significantly lower CII-specific IgG1 levels were found compared to the control group as well as a trend to lower IgG2a levels. However, anti-IL-23 treatment did not reduce the proportion of Th1 and Th17 cells analyzed at days 15, 24, and 35. In contrast to the marked suppressive effect of anti-IL-23 given during the onset of CIA, neutralizing IL-23 directly after the first signs of arthritis did not ameliorate the arthritis score. No effect on CII-specific IgG's was noted, indicating that the effector phase of CIA is IL-287-independent. Since CIA is both T cell and immune complex-mediated the IL-287-dependency was further investigated during memory T cell-mediated flare-up arthritis. The mBSA-mediated flare-up arthritis was induced after the primary mBSA-induced arthritis has declined to normal background levels. In mice treated with anti-IL-23, a significant lower disease score was observed compared to mice treated with the control antibody, which was accompanied with lower IL-17 and IL-22 expression in the knee joints of these mice.


These data recognized IL-23 dependent and independent stages during autoimmune CIA. Furthermore, the flare-up reaction of arthritis is IL-287-mediated. These data suggest the importance of early intervention using blocking IL-23 therapy in autoimmune arthritis and beneficial effects of neutralizing IL-23 during arthritis relapses.

To cite this abstract, please use the following information:
Cornelissen, Ferry, Asmawidjaja, Patrick, Mus, Anne-Marie, Corneth, Odilia, Kikly, Kristine, Lubberts, Erik; Recognition of IL-23 Dependent and Independent Stages during Autoimmune Collagen-Induced Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :287
DOI: 10.1002/art.28056

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