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- Open Access
TNF-α dependency of IL-17-induced joint pathology differs under naive and arthritis conditions in vivo
Arthritis Res Ther volume 5, Article number: 46 (2003)
T-cell IL-17 is a proinflammatory cytokine present in the synovium of RA patients. IL-17 is an inducer of other cytokines, such as IL-1 and TNF. It can have both additive and synergistic effects on cytokine induction and tissue destruction with these cytokines, but may have direct pathological effects as well.
Objective and methods
In the present study, we examined the dependency of TNF-α in the IL-17-induced joint inflammation and cartilage damage under naive and arthritis conditions using an adenoviral vector expressing mIL-17 (AdIL-17).
IL-17 overexpression in the knee joint of naive mice resulted in joint inflammation and cartilage proteoglycan depletion, which gradually increased with time. No effects were noted with the same dose of the control vector. IL-17 induced elevated expression of IL-1 mRNA levels in the synovium in comparison with the control group. However, no difference in IL-17-induced joint pathology was noted in IL-1α/β-deficient mice. Of high interest, using TNF-α deficient mice, the IL-17-induced joint inflammation and cartilage damage were almost completely absent. This strongly indicates that under naive conditions in vivo the IL-17-induced joint inflammation and cartilage destruction are mediated by TNF and not necessarily by IL-1.
Since it is known that in streptococcal-cell-wall (SCW) arthritis, TNF and IL-1 induction can be uncoupled, we did similar experiments in this acute SCW arthritis model. Overexpression of T-cell IL-17 in this macrophage-mediated model results in an elevation of joint inflammation and cartilage proteoglycan depletion in comparison with the control vector group. Furthermore, this T-cell cytokine turns this acute model into a more chronic one. Although knocking out TNF-α did have some effect on inflammation and cartilage damage, the dependency of TNF in IL-17 induced pathology was not as strong as under naive conditions.
These data show a direct relation of IL-17 and TNF-α induction under naive conditions in vivo. However, the presence of IL-1 during arthritis conditions and the collaboration of IL-17 with IL-1 modulates the TNF-α dependency during arthritis.
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Koenders, M., Lubberts, E., Joosten, L. et al. TNF-α dependency of IL-17-induced joint pathology differs under naive and arthritis conditions in vivo. Arthritis Res Ther 5, 46 (2003) doi:10.1186/ar676
- Cartilage Damage
- Joint Inflammation
- Vector Group
- Cytokine Induction
- Naive Mouse