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