IL-18 inhibits TNF-α-induced osteoclastogenesis possibly via a T cell-independent mechanism in synergy with IL-12 in vivo

Yukiko Morita, Hideki Kitaura, Masako Yoshimatsu, Yuji Fujimura, Haruka Kohara, Toshiko Eguchi, Noriaki Yoshida

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31 Citations (Scopus)


It has recently been reported that tumor necrosis factor (TNF)-a has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine interleukin (IL)-18 inhibits TNF-α-mediated osteoclastogenesis in mouse bone marrow cultures. In the present study, the effect of IL-18 on TNF-α-mediated osteoclastogenesis was investigated in vivo. We administered TNF-α with or without IL-18 into the supracalvaria of mice. The number of osteoclasts in the suture of the calvaria was increased in mice administered TNF-α. The number of osteoclasts in mice administered both TNF-α and IL-18 was lower than that in mice administered TNF-α alone. We previously showed that IL-12 and IL-18 synergistically inhibit TNF-α-mediated osteoclastogenesis in vitro. To assess the ability of these two cytokines to synergistically inhibit TNF-α-induced osteoclastogenesis in vivo, mice were administered the two cytokines at doses that did not inhibit osteoclast formation. The combination of IL-12 and IL-18 markedly inhibited TNF-α-induced osteoclastogenesis in vivo. To evaluate how IL-12 and IL-18 synergistically affect TNF-α-induced osteoclastogenesis, the IL-18 receptor (IL-18R) and IL-12R expression levels were analyzed by RT-PCR in bone marrow cells cultured with IL-12 or IL-18. IL-18R mRNA was increased in cells cultured with IL-12, while IL-12R mRNA was increased in cells cultured with IL-18. In addition, IL-18 inhibited TNF-α-induced osteoclastogenesis in mice with T-cell depletion caused by anti-CD4 and anti-CD8 antibodies. The present results suggest that IL-18 may inhibit TNF-α-mediated osteoclastogenesis in vivo via a T cell-independent mechanism.

Original languageEnglish
Pages (from-to)242-248
Number of pages7
JournalCalcified Tissue International
Issue number3
Publication statusPublished - 2010 Mar


  • IL-12
  • IL-18
  • Osteoclast
  • TNF-α

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology


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