THE EFFECTS OF IL-1-BETA AND IL-4 ON THE PROLIFERATION AND ENDOGENOUS SECRETION OF GROWTH-FACTORS BY ACUTE MYELOBLASTIC LEUKEMIC-CELLS

The effects of interleukin-1beta (IL-1) and IL-4 were studied on the proliferation of acute myeloid leukemia (AML) cells. IL-1 stimulated tritiated thymidine (H-3-TdR) uptake of AML cells in 8/12 cases, whereas IL-4 enhanced H-3-TdR uptake in 5/12. Combination of both factors resulted in an additive effect in 6/12 cases which could be abrogated by the addition of anti-granulocyte-macrophage colony stimulating factor (GM-CSF). To study whether IL-1, IL-4, or IL-1 plus IL-4 affects the AML progenitor cell directly or indirectly by the release of endogenous factors, supernatants of stimulated AML cells (n = 6) were analyzed for GM-CSF, IL-6, and tumor necrosis factor-alpha (TNF) production. IL-1 induced the endogenous secretion of GM-CSF, IL-6, and TNF in most cases. In contrast, no secretion of growth factors was induced by IL-4, whereas in 2 cases IL-4 suppressed the IL-1-induced secretion of GM-CSF, TNF, and IL-6. This was associated with a decline in the proliferative response to IL-1 measured in a clonogenic assay. In addition it was shown that exogeneous supplied GM-CSF and TNF could raise the suppressive effects of ILA on the IL-1-supported proliferation. In summary these data indicate that the ILA-supported proliferation is not caused by the endogenous secretion of GM-CSF, IL-6, and TNF. Furthermore the suppressive effect of IL-4 on the IL-1-induced proliferation in some cases may be caused by a reduced secretion of GM-CSF, TNF, and IL-6.