Interleukin-4 and interleukin-13: bidirectional effects on human osteoclast formation

• Published in: Bone (New York, N.Y.) N.Y.), 2001-09, Vol.29 (3), p.203-208
• Main Authors: Scopes, J, Massey, H.M, Ebrahim, H, Horton, M.A, Flanagan, A.M
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Biological and medical sciences; Carrier Proteins - pharmacology; Cell Communication - immunology; Cell Count; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Human; Humans; Interleukin-13; Interleukin-13 - pharmacology; Interleukin-4; Interleukin-4 - pharmacology; Macrophages - cytology; Membrane Glycoproteins - pharmacology; Monocytes - cytology; Monocytes/macrophages; Osteoclast; Osteoclasts - cytology; Osteoclasts - drug effects; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Skeleton and joints; Th1 Cells - cytology; Th1/Th2; Th2 Cells - cytology; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/S8756-3282(01)00500-2

Osteoclasts are cells that resorb bone; they derive from macrophage colony-stimulating factor (M-CSF)-dependent hematopoietic precursors in the presence of soluble activator of NFκB ligand (sRANKL). Because transforming growth factor (TGF)-β, a macrophage deactivator, enhances osteoclast formation we hypothesized that interleukin (IL)-4 and IL-13, also macrophage deactivators, should exert a similar effect. However, IL-4 and IL-13 have been reported as suppressors of murine osteoclast formation. In contrast to the effect of these molecules on murine osteoclast formation, IL-4 and IL-13 were found to be powerful inducers of osteoclast formation and bone resorption when added to human peripheral blood mononuclear cell (PBMC) cultures for 4 days. This stimulatory effect was only observed in cultures containing nonadherent PBMCs. In contrast, both molecules significantly suppressed osteoclast formation in lymphocyte-depleted cultures. These data demonstrate that the cytokine milieu and/or state of cell activation determines how cells of the osteoclast precursor respond to IL-4 and IL-13.