Interleukin-17 acts independently of TNF-alpha under arthritic conditions
Koenders, M.I.; Lubberts, E.; van de Loo, F.A.J.; Oppers-Walgreen, B.; van den Bersselaar, L.; Helsen, M.M.; Kolls, J.K.; Di Padova, F.E.; Joosten, L.A.B.; van den Berg, W.B.
Journal of Immunology 176(10): 6262-6269
2006
ISSN/ISBN: 0022-1767 PMID: 16670337 Document Number: 602942
The proinflammatory T cell cytokine IL-17 is a potent inducer of other cytokines such as IL-1 and TNF-alpha. The contribution of TNF in IL-17-induced joint inflammation is unclear. In this work we demonstrate using TNF-alpha-deficient mice that TNF-a is required in IL-17-induced joint pathology under naive conditions in vivo. However, overexpression of IL-17 aggravated K/BxN serum transfer arthritis to a similar degree in TNF-a-deficient mice and their wild-type counterparts, indicating that the TNF dependency of IL-17-induced pathology is lost under arthritic conditions. Also, during the course of the streptococcal cell wall-induced arthritis model, IL-17 was able to enhance inflammation and cartilage damage in the absence of TNF. Additional blocking of IL-1 during IL-17-enhanced streptococcal cell wall-induced arthritis did not reduce joint pathology in TNF-deficient mice, indicating that IL-1 is not responsible for this loss of TNF dependency. These data provide further understanding of the cytokine interplay during inflammation and demonstrate that, despite a strong TNF dependency under naive conditions, IL-17 acts independently of TNF under arthritic conditions.