AUGMENTED PRODUCTION OF INTERLEUKIN-6 BY NORMAL HUMAN OSTEOBLASTS IN RESPONSE TO CD34(-MARROW CELLS IN-VITRO() HEMATOPOIETIC BONE)

Based on anatomic and developmental findings characterizing hematopoie tic cells in close approximation with endosteal cells, we have begun a n analysis of osteoblast/hematopoietic cell interactions. We explore h ere the functional interdependence between these two cell types from t he standpoint of de novo cytokine secretion. We determined that, over a 96-hour period, CD34(+) bone marrow cells had no significant effect on osteoblast secretion of granulocyte colony-stimulating factor, gran ulocyte-macrophage colony-stimulating factor, or transforming growth f actor-beta(1), but in some experiments minor increases in leukemia inh ibitory factor levels were observed. However, when CD34(+) bone marrow cells were cocultured in direct contact with osteoblasts, a 222% +/- 55% (range, 153% to 288%) augmentation in interleukin-6 (IL-6) synthes is was observed. The accumulation of IL-6 protein was most rapid durin g the initial 24-hour period, accounting for nearly 55% of the total I L-6 produced by osteoblasts in the absence of blood cells and 77% of t he total in the presence of the CD34(+) cells. Cell-to-cell contact do es not appear to be required for this activity, as determined by cocul turing the two cell types separated by porous micromembranes. The iden tity of the soluble activity produced by the CD34(+) cells remains unk nown, but is not likely due to IL-1 beta or tumor necrosis factor-alph a, as determined with neutralizing antibodies. To our knowledge, these data represent the first demonstration that early hematopoietic cells induce the production of molecules required for the function of norma l bone marrow microenvironments, in this case through the induction of hematopoietic cytokine (IL-6) secretion by osteoblasts. (C) 1997 by T he American Society of Hematology.