Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Critical Role for the IL-23/TNF Axis During TLR2/NOD2 Mediated Acute Joint Inflammation.

Cornelissen1,  Ferry, Corneth2,  Odilia B.J., Mus1,  Anne-Marie, Asmawidjaja1,  Patrick S., Lubberts1,  Erik

Erasmus MC, University Medical Center, Rotterdam, Netherlands
Erasmus MC, University Medical Center, Rotterdam, Rotterdam, Netherlands

Background/Purpose:

IL-23 is essential in the development of chronic autoimmune diseases and supports the maturation of pathogenic Th17 cells. Although the role of IL-23 during adaptive immunity in arthritis has been studied extensively, the role of IL-23 during acute joint inflammation is unknown. Therefore, the purpose of this study is to investigate the role of IL-23 in the development of an acute, macrophage-mediated joint inflammation.

Methods:

Peptidoglycan (PG) or streptococcal cell wall fragments (SCW) were intra-articularly injected into the knee joint of naïve wt or IL-23p19-deficient mice. Joint swelling was assessed by measuring joint thickness using a caliper. In addition, synovial expression of different cytokines was measured by specific ELISA and/or Q-PCR. Moreover, synovial explants of wt and IL-23p19-deficient mice were stimulated with SCW and cytokine levels were measured by ELISA.

Results:

TLR2/NOD2-mediated streptococcal cell wall (SCW) and peptidoglycan (PG) induced acute joint inflammation in IL-23p19-deficient mice resulted in a profound reduction of local joint inflammation compared to control mice in both these models. Synovial IL-23p19 transcript was detected at 1.5 and 4 hours after arthritis induction and was further increased 1 day after PG injection with a peak at day 2. Interestingly, IL-23p19-deficient mice showed a significant reduction in synovial TNFalpha, but not IL-6 levels 4 hours after TLR2/NOD2-mediated arthritis induction in the knee joint. In line with this, reduced TNFalpha levels were detected in the culture supernatant of SCW-stimulated synovial explants from IL-23p19-deficient mice compared to control mice.

Conclusion:

These data show a critical role for IL-23 in the development of a TLR2/NOD2-mediated acute joint inflammation and reveal a novel IL-23/TNFalpha axis in this process.

To cite this abstract, please use the following information:
Cornelissen, Ferry, Corneth, Odilia B.J., Mus, Anne-Marie, Asmawidjaja, Patrick S., Lubberts, Erik; Critical Role for the IL-23/TNF Axis During TLR2/NOD2 Mediated Acute Joint Inflammation. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :50
DOI:

Abstract Supplement

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