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Kitaura, H, Nagata, N, Fujimura, Y, Hotokezaka, H, Tatamiya, M, Nakao, N, Yoshida, N and Nakayama, K (2003) Interleukin-4 directly inhibits tumor necrosis factor-alpha-mediated osteoclast formation in mouse bone marrow macrophages. Immunol. Lett. 88:193-8


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.




Acid Phosphatase/metabolism; Animals; Bone Marrow/drug effects; Bone Resorption; Carrier Proteins/pharmacology; Cell Differentiation/drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Humans; Interleukin-4/pharmacology; Isoenzymes/metabolism; Macrophage Colony-Stimulating Factor/pharmacology; Macrophages/cytology; Macrophages/drug effects; Membrane Glycoproteins/pharmacology; Mice; Osteoclasts/cytology; Osteoclasts/drug effects; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Tumor Necrosis Factor-alpha/antagonists & inhibitors; Tumor Necrosis Factor-alpha/pharmacology



Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status

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