Arthritis Res Ther

, 6:30 | Cite as

IL-1-dependent cartilage damage in a macrophage-driven arthritis model can be circumvented by T cell IL-17

  • MI Koenders
  • E Lubberts
  • LAB Joosten
  • JK Kolls
  • WB van den Berg
Meeting abstract
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Keywords

Rheumatoid Arthritis Arthritis Rheumatoid Arthritis Patient Knee Joint Adenoviral Vector 

Background

In the murine macrophage-mediated SCW-induced arthritis, IL-1 plays a dominant role in cartilage destruction, as was shown in previous studies using cytokine gene knockout mice or antibodies against IL-1. T cell IL-17 is a proinflammatory cytokine that has many IL-1-like activities. IL-17 is expressed in the synovium of RA patients and may play a role in rheumatoid arthritis (RA) pathology.

Objective

In the present study we examined the potency of T cell IL-17 to bypass the relative IL-1 dependency of cartilage damage during macrophage-driven SCW-induced arthritis.

Methods

SCW-arthritis was induced in IL-1 deficient mice and their C57Bl/6 controls by intra-articular injection of 25 μg SCW fragments. Sixteen hours before the induction of arthritis, an adenoviral vector expressing murine IL-17 or a control virus was injected into the knee joint. Total knee joints were isolated for histological analysis of joint inflammation by H&E staining and cartilage damage was measured as proteoglycan (PG) depletion by Safranin O staining.

Results

During SCW-induced arthritis, cartilage damage was clearly suppressed in IL-1 deficient mice. Overexpression of T cell IL-17 in the SCW arthritis model caused aggravation of the synovial inflammation and induces more severe PG depletion. IL-1-/- mice showed the same influx of inflammatory cells and comparable degree of cartilage damage as control mice (Fig. 1), indicating that overexpression of IL-17 causes loss of IL-1 dependency in this model.
Figure 1

PG depletion 10 days after induction of SCW arthritis, in combination with the ia injection of control virus or AdIL-17.

Discussion

These data show circumvention of the IL-1 dependency of cartilage damage by T cell IL-17 in the macrophage-driven SCW arthritis model. IL-1 and its receptor share the same signaling pathway through TRAF-6 and NF-κB as IL-17. These data suggest that T cell IL-17 can replace the catabolic function of IL-1 regarding cartilage damage, directly or via interplay with other macrophage-driven factors.

Copyright information

© The Author(s) 2004

Authors and Affiliations

  • MI Koenders
    • 1
  • E Lubberts
    • 1
  • LAB Joosten
    • 1
  • JK Kolls
    • 2
  • WB van den Berg
    • 1
  1. 1.Experimental Rheumatology and Advanced TherapeuticsUniversity Medical Center NijmegenNijmegenThe Netherlands
  2. 2.Department of MedicineLouisiana State UniversityNew OrleansUSA

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