Interleukin-17 acts independently of TNF-α under arthritic conditions

被引:97
作者
Koenders, Marije I.
Lubberts, Erik
van De Loo, Fons A. J.
Oppers-Walgreen, Birgitte
van den Bersselaar, Liduine
Helsen, Monique M.
Kolls, Jay K.
Di Padova, Franco E.
Joosten, Leo A. B.
van den Berg, Wim B.
机构
[1] Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands
[2] Childrens Hosp Pittsburgh, Dept Pediat & Pulm, Pittsburgh, PA 15213 USA
[3] Novartis Inst Biomed Res, Basel, Switzerland
关键词
D O I
10.4049/jimmunol.176.10.6262
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:6262 / 6269
页数:8
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