Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

TNF-Induced Structural Joint Damage Is Mediated by IL-1

Jochen Zwerina, Kurt Redlich, Karin Polzer, Leo Joosten, Gerhard Kroenke, Joerg Distler, Andreas Hess, Noreen Pundt, Thomas Pap, Oskar Hoffmann, Juerg Gasser, Clemens Scheinecker, Josef S. Smolen, Wim van den Berg and Georg Schett
Proceedings of the National Academy of Sciences of the United States of America
Vol. 104, No. 28 (Jul. 10, 2007), pp. 11742-11747
Stable URL: http://www.jstor.org/stable/25436189
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
TNF-Induced Structural Joint Damage Is Mediated by IL-1
Preview not available

Abstract

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 $({\rm IL}\text{-}1^{-/-})$ 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 ${\rm IL}\text{-}1^{-/-}{\rm hTNFtg}$ mice, compared with hTNFtg mice based on an intrinsic differentiation defect of IL-1-deficient monocytes. Most dramatically, however, cartilage damage was absent in ${\rm IL}\text{-}1^{-/-}{\rm hTNFtg}$ 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.

Page Thumbnails

  • Thumbnail: Page 
11742
    11742
  • Thumbnail: Page 
11743
    11743
  • Thumbnail: Page 
11744
    11744
  • Thumbnail: Page 
11745
    11745
  • Thumbnail: Page 
11746
    11746
  • Thumbnail: Page 
11747
    11747