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

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Ferry Cornelissen1, Odilia B.J. Corneth2, Anne-Marie Mus1, Patrick S. Asmawidjaja1 and Erik Lubberts1, 1Erasmus MC, University Medical Center, Rotterdam, Netherlands, 2Erasmus MC, University Medical Center, Rotterdam, Rotterdam, Netherlands
Presentation Number: 50

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.

Method: 

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.

Result: 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.


Keywords: animal models, cytokines and inflammation

Disclosure: F. Cornelissen, None; O. B. J. Corneth, None; A. M. Mus, None; P. S. Asmawidjaja, None; E. Lubberts, None.