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

• Published in: Journal of Immunology Vol. 176; no. 10; pp. 6262 - 6269
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 15.05.2006
• Subjects: Animals; Arthritis, Experimental - immunology; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Genetic Vectors - administration & dosage; Interleukin-17 - administration & dosage; Interleukin-17 - biosynthesis; Interleukin-17 - genetics; Interleukin-17 - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Streptococcus; Tumor Necrosis Factor-alpha - deficiency; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.10.6262

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.