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Immunol Lett. 2003 Sep 8;88(3):193-8.

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

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  • 1Division of Orthodontic and Biomedical Engineering, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.


Recently it has been found that osteoclast differentiation is induced by tumor necrosis factor (TNF)-alpha. Interleukin (IL)-4 was reported to suppress osteoclast differentiation and bone resorption. However, no study has investigated the effect of IL-4 on TNF-alpha-induced osteoclast formation. In this study, we investigated whether IL-4 inhibits TNF-alpha-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-alpha, osteoclast-like cells were formed. When they were cultured with both TNF-alpha 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-alpha and RANKL synergistically promote osteoclastogenesis. Finally, we investigated whether IL-4 had the ability to inhibit synergistic TNF-alpha 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-alpha.

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