Interleukin 4 alters human bone marrow stroma and modulates its interaction with hematopoietic progenitors

To investigate the functional activity of interleukin 4 (IL‐4) on human marrow stroma formation, normal bone marrow (BM) samples were cultured in “Dexter‐type” long‐term cultures in the presence and absence of IL‐4. IL‐4 (0.001 to 1.0 μg/ml) added at the initiation of culture and once weekly when the cultures were fed effaced the culture architecture. In four‐week old confluent cultures smooth muscle‐like and endothelial‐like cells were rare, the fibronectin network and cobblestone areas were absent, and a preponderance of monocyte‐macrophages characterized the adherent layer. Exposure to IL‐4 reduced the numbers of CD34⁺ cells, colony‐forming unit granulocyte‐macrophage (GFU‐GM) cells and burst‐forming unit‐erythroid (BFU‐E) cells in the adherent layer, and increased their numbers in the nonadherent layer. In five of eight IL‐4‐containing cultures the concentrations of macrophage colony‐stimulating factor (M‐CSF) were increased and in two of eight IL‐4‐treated cultures the concentrations of tumor necrosis factor‐α (TNF‐α) were significantly elevated as compared to those in control cultures, whereas there were no consistent differences in the levels of either IL‐6 or transforming growth factor‐β (TGF‐β). IL‐1β and granulocyte‐macrophage CSF (GM‐CSF) were not detected in any culture. These data suggest that IL‐4 suppresses stroma formation and alters its structure and cellular composition.