IL-12 alone and in synergy with IL-18 inhibits osteoclast formation in vitro

Horwood, Nicole J. ORCID:, Elliott, Jan, Martin, T. John and Gillespie, Matthew T. (2001) IL-12 alone and in synergy with IL-18 inhibits osteoclast formation in vitro. Journal of Immunology, 166 (8). pp. 4915-4921. ISSN 0022-1767

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IL-12, like IL-18, was shown to potently inhibit osteoclast formation in cultures of cocultures of murine osteoblast and spleen cells, as well as in adult spleen cells treated with M-CSF and receptor activator of NF-kappaB ligand (RANKL). Neither IL-12 nor IL-18 was able to inhibit RANKL-induced osteoclast formation in cultured RAW264.7 cells, demonstrating that IL-12, like IL-18, was unable to act directly on osteoclastic precursors. IL-12, like IL-18, was found to act by T cells, since depletion of T cells from the adult spleen cell cultures ablated the inhibitory action of IL-12 and addition of either CD4 or CD8 T cells from C57BL/6 mice to RANKL-stimulated RAW264.7 cultures permitted IL-12 or IL-18 to be inhibitory. Additionally, IL-12 was still able to inhibit osteoclast formation in cocultures with osteoblasts and spleen cells from either GM-CSF R(-/-) mice or IFN-gamma R(-/-) mice, indicating that neither GM-CSF nor IFN-gamma was mediating osteoclast inhibition in these cultures. Combined, IL-18 and IL-12 synergistically inhibited osteoclast formation at concentrations 20- to 1000-fold less, respectively, than when added individually. A candidate inhibitor could not be demonstrated using neutralizing Abs to IL-4, IL-10, or IL-13 or from mRNA expression profiles among known cytokine inhibitors of osteoclastogenesis in response to IL-12 and IL-18 treatment, although the unknown inhibitory molecule was determined to be secreted from T cells.

Item Type: Article
Uncontrolled Keywords: animals,instrumentation,immunology,cell line,cells, cultured,coculture techniques,immunology,drug combinations,drug synergism,metabolism,metabolism,metabolism,metabolism,metabolism,male,mice,mice, inbred c57bl,mice, knockout,cytology,deficiency,deficiency,immunology
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 06 Mar 2019 09:30
Last Modified: 19 Oct 2023 02:22
DOI: 10.4049/jimmunol.166.8.4915

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