Interleukin-17 acts independently of TNF-alpha under arthritic conditions.
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-alpha 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-alpha-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.
Koenders
Marije I
MI
Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands. m.koenders@reuma.umcn.nl
Lubberts
Erik
E
van de Loo
Fons A J
FA
Oppers-Walgreen
Birgitte
B
van den Bersselaar
Liduine
L
Helsen
Monique M
MM
Kolls
Jay K
JK
Di Padova
Franco E
FE
Joosten
Leo A B
LA
van den Berg
Wim B
WB