Advertisement

Research Article Free access | 10.1172/JCI1333

Interleukin 18 inhibits osteoclast formation via T cell production of granulocyte macrophage colony-stimulating factor.

N J Horwood, N Udagawa, J Elliott, D Grail, H Okamura, M Kurimoto, A R Dunn, T Martin, and M T Gillespie

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Horwood, N. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Udagawa, N. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Elliott, J. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Grail, D. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Okamura, H. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Kurimoto, M. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Dunn, A. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Martin, T. in: JCI | PubMed | Google Scholar

St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.

Find articles by Gillespie, M. in: JCI | PubMed | Google Scholar

Published February 1, 1998 - More info

Published in Volume 101, Issue 3 on February 1, 1998
J Clin Invest. 1998;101(3):595–603. https://doi.org/10.1172/JCI1333.
© 1998 The American Society for Clinical Investigation
Published February 1, 1998 - Version history
View PDF
Abstract

IL-18 inhibits osteoclast (OCL) formation in vitro independent of IFN-gamma production, and this was abolished by the addition of neutralizing antibodies to GM-CSF. We now establish that IL-18 was unable to inhibit OCL formation in cocultures using GM-CSF-deficient mice (GM-CSF -/-). Reciprocal cocultures using either wild-type osteoblasts with GM-CSF -/- spleen cells or GM-CSF -/- osteoblasts with wild-type spleen cells were examined. Wild-type spleen cells were required to elicit a response to IL-18 indicating that cells of splenic origin were the IL-18 target. As T cells comprise a large proportion of the spleen cell population, the role of T cells in osteoclastogenesis was examined. Total T cells were removed and repleted in various combinations. Addition of wild-type T cells to a GM-CSF -/- coculture restored IL-18 inhibition of osteoclastogenesis. Major subsets of T cells, CD4+ and CD8+, were also individually depleted. Addition of either CD4+ or CD8+ wild-type T cells restored IL-18 action in a GM-CSF -/- background, while IL-18 was ineffective when either CD4+ or CD8+ GM-CSF -/- T cells were added to a wild-type coculture. These results highlight the involvement of T cells in IL-18-induced OCL inhibition and provide evidence for a new OCL inhibitory pathway whereby IL-18 inhibits OCL formation due to action upon T cells promoting the release of GM-CSF, which in turn acts upon OCL precursors.

Version history
  • Version 1 (February 1, 1998): No description
Advertisement
Advertisement