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

Journal article

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.

Authors: Horwood, N; Elliott, J; Martin, T; Gillespie, M

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 166
• Issue: 8
• Pages: 4915-4921
• Publication date: 2001-04-01
• DOI: 10.4049/jimmunol.166.8.4915
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Cell Line; Mice, Inbred C57BL; Growth Inhibitors; Osteoclasts; Interleukin-12; T-Lymphocytes; Cell Differentiation; Cells, Cultured; Drug Combinations; Interleukin-18; Receptors, Interferon; Drug Synergism; Mice; Interferon-gamma; Coculture Techniques; Animals; Mice, Knockout; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Down-Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Male; Cell Culture Techniques