Augmented production of interleukin 6 by co-culture of human bone marrow adherent cells and human leukemic cells.
Human Dexter-type culture of bone marrow (BM) cells maintains long-term hematopoiesis in the presence of an adherent stromal layer. These BM adherent cells produce hematopoietic growth factors constitutively or inducively and support developing hematopoietic cells. To elucidate the ability of cytokine production by BM adherent cells, the cytokine levels of the culture supernatant of BM adherent cells were measured by enzyme-linked immunosorbent assays. Constitutive production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL-6) by the unstimulated BM adherent cells was demonstrated. Levels of granulocyte colony-stimulating factor (G-CSF) were below detectable levels (< 10 pg/ml). The IL-6 level was significantly increased in the co-culture supernatant with KG1 cells or U937 cells (P < 0.01: P < 0.05, respectively). Even when the adherent cells and cell line cells were separated by a membrane filter, the IL-6 level was significantly higher than the control culture (P < 0.01). Co-culture with these cell lines was supposed to induce the increased production of IL-6, which was mediated by some soluble cytokines. The GM-CSF level was not increased in the supernatant co-cultured with any of the cell lines, except with K562 cells. However, K562 cells alone secreted a detectable level of GM-CSF and the increased level of GM-CSF was considered to be due to the production of GM-CSF by K562 cells. G-CSF was not detectable in the supernatant co-cultured with any cell line cells. This result indicates that the cytokine production was regulated by the interaction of BM adherent cells and some leukemic cells.