Details

Autor(en) / Beteiligte

• Zwerina, Jochen
• Redlich, Kurt
• Polzer, Karin
• Joosten, Leo
• Krönke, Gerhard
• Distler, Joerg
• Hess, Andreas
• Pundt, Noreen
• Pap, Thomas
• Hoffmann, Oskar
• Gasser, Juerg
• Scheinecker, Clemens
• Smolen, Josef S
• van den Berg, Wim
• Schett, Georg

Titel

TNF-induced structural joint damage is mediated by IL-1

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2007-07, Vol.104 (28), p.11742-11747

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• Blocking TNF effectively inhibits inflammation and structural damage in human rheumatoid arthritis (RA). However, so far it is unclear whether the effect of TNF is a direct one or indirect on up-regulation of other mediators. IL-1 may be one of these candidates because it has a central role in animal models of arthritis, and inhibition of IL-1 is used as a therapy of human RA. We removed the effects of IL-1 from a TNF-mediated inflammatory joint disease by crossing IL-1α and β-deficient mice (IL-1⁻/⁻) with arthritic human TNF-transgenic (hTNFtg) mice. Development of synovial inflammation was almost unaffected on IL-1 deficiency, but bone erosion and osteoclast formation were significantly reduced in IL-1⁻/⁻hTNFtg mice, compared with hTNFtg mice based on an intrinsic differentiation defect of IL-1-deficient monocytes. Most dramatically, however, cartilage damage was absent in IL-1⁻/⁻hTNFtg mice. Chimera studies revealed that protection of cartilage is based on the loss of IL-1 on hematopoietic, but not mesenchymal, cells, leading to decreased expression of ADAMTS-5 and MMP-3. These data show that TNF-mediated cartilage damage is completely and TNF-mediated bone damage is partially dependent on IL-1, suggesting that IL-1 is a crucial mediator for inflammatory cartilage and bone degradation.