Volume 5 Supplement 1

23rd European Workshop for Rheumatology Research

Open Access

Endogenous IL-12p40 is crucial for antigen-induced arthritis and is partly involved in chronic relapsing streptococcal-cell-wall arthritis

  • M Jacobs1,
  • L Joosten1,
  • MMA Helsen1,
  • E Lubberts1 and
  • WB van den Berg1
Arthritis Res Ther20035(Suppl 1):42

https://doi.org/10.1186/ar672

Received: 14 January 2003

Published: 24 February 2003

Background

Interleukin 12 (IL-12) is a proinflammatory cytokine with important immunoregulatory activities and is critical in determining the differentiation and generation of Th1 cells.

Objectives

For the present study, we investigated the role of endogenous IL-12p40, component of both IL-12 and IL-23, in the pathogenesis of antigen- and chronic relapsing streptococcal-cell-wall-(SCW-) induced arthritis. To this end we used C57Bl6 (wild-type; WT) and IL-12p40-deficient (IL-12 ko) mice. Chronic SCW was induced by intra-articular (i.a.) injection of 25 μg SCW fragments at days 0, 7, 14 and 21. Joint swelling and histology were examined at day 28 after the first injection. Antigen-induced arthritis (AIA) was initiated by i.a. injection of 60 μg mBSA in preimmunized mice. Joint swelling was measured at days 3, 7 and 14, whereas histology was examined at days 7 and 14.

Results

At day 28, joint swelling of the mainly macrophage-driven chronic SCW arthritis was significantly reduced in IL-12p40 ko mice in comparison with WT mice (P = 0.0008). Although cell influx was decreased (P = 0.0194), no reduction in cartilage proteoglycan depletion was found. In a predominantly T-cell-mediated process such as AIA, joint swelling was significantly suppressed at days 3 and 7 in IL-12p40 ko mice in comparison with WT (P = 0.0021 and P = 0.0260 respectively). Moreover, histopathology was drastically reduced in IL-12p40 ko mice; the number of inflammatory cells was strongly suppressed in IL-12p40 ko mice in comparison with WT animals (1.6 ± 0.4 vs 0.2 ± 0.2 and P < 0.0001). In line with these findings matrix proteoglycan depletion was completely absent in IL-12p40 ko mice (1.9 ± 0.35 vs 0.05 ± 0.11 and P < 0.0001).

Conclusion

These results indicate that IL-12p40 plays a pivotal role in antigen-induced arthritis and a minor role in chronic relapsing streptococcal-cell-wall-induced arthritis.

Authors’ Affiliations

(1)
Rheumatology Research Laboratory, University Medical Center Nijmegen

Copyright

© The Author(s) 2003

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