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

Horwood, N J, Udagawa, N, Elliott, J, Grail, D, Okamura, H, Kurimoto, M, Dunn, A R, Martin, T and Gillespie, M T (1998) Interleukin 18 inhibits osteoclast formation via T cell production of granulocyte macrophage colony-stimulating factor. Journal of Clinical Investigation, 101 (3). pp. 595-603. ISSN 0021-9738

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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.

Item Type: Article
Uncontrolled Keywords: animals,drug effects,drug effects,cells, cultured,pharmacology,biosynthesis,pharmacology,interleukin-18,mice,mice, inbred c57bl,mice, knockout,cytology,drug effects
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Medicine and Health Sciences > School of Nursing and Midwifery
Faculty of Science > School of Biological Sciences
Depositing User: LivePure Connector
Date Deposited: 06 Mar 2019 09:30
Last Modified: 22 Apr 2020 07:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/70113
DOI: 10.1172/JCI1333

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