Interleukin-4 directly inhibits tumor necrosis factor-α-mediated osteoclast formation in mouse bone marrow macrophages

Hideki Kitaura, Noriko Nagata, Yuji Fujimura, Hitoshi Hotokezaka, Mutsuhito Tatamiya, Noriko Nakao, Noriaki Yoshida, Koji Nakayama

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23 Citations (Scopus)


Recently it has been found that osteoclast differentiation is induced by tumor necrosis factor (TNF)-α. Interleukin (IL)-4 was reported to suppress osteoclast differentiation and bone resorption. However, no study has investigated the effect of IL-4 on TNF-α-induced osteoclast formation. In this study, we investigated whether IL-4 inhibits TNF-α-mediated osteoclast formation in mouse bone marrow derived macrophages (BMM). First, IL-4 suppresses RANKL-induced osteoclast formation and bone resorption. Next, when BMM were cultured with TNF-α, osteoclast-like cells were formed. When they were cultured with both TNF-α and IL-4, osteoclast formation and bone resorption was suppressed by IL-4 in a dose-dependent manner. It has been recently found that TNF-α and RANKL synergistically promote osteoclastogenesis. Finally, we investigated whether IL-4 had the ability to inhibit synergistic TNF-α and RANKL-induced osteoclastogenesis, with the result that it effectively inhibited the synergistic osteoclast formation in a dose-dependent manner. We conclude that IL-4 can strongly inhibit osteoclast formation that is related to both physiological bone resorption induced by RANKL and pathological bone resorption induced by TNF-α.

Original languageEnglish
Pages (from-to)193-198
Number of pages6
JournalImmunology Letters
Issue number3
Publication statusPublished - 2003 Sep 8
Externally publishedYes


  • IL-4
  • Osteoclast
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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