INHIBITORY EFFECT OF INTERLEUKIN-4 ON THE PROLIFERATION OF ACUTE MYELOID-LEUKEMIA CELLS WITH MYELO-MONOCYTIC DIFFERENTIATION (AML-M4 M5) - THE ROLE OF INTERLEUKIN-6/

Since interleukin-4 (IL-4) specifically inhibits monocytic colony form ation in human bone marrow cultures, we investigated whether a similar inhibition could be observed in cultures of optimally stimulated acut e myeloid leukemia cells with myelo-monocytic differentiation (AML-M4/ M5). Sensitivity to IL-4 was tested in 19 cases of AML-M4/M5, using bo th a H-3-thymidine incorporation assay and a clonogenic assay. Prolife ration was stimulated with a combination of IL-3, granulocyte-monocyte colony-stimulating factor (GM-CSF), and conditioned medium from phyto hemagglutinin-stimulated leukocytes (PHA-CM). In 13 out of 14 evaluabl e cases, IL-4 inhibited H-3-thymidine incorporation; stimulation was s een in one cass. Using a clonogenic assay, IL-4 inhibited colony forma tion in all evaluable cases (n = 7). Addition of IL-6 did not alter th e observed inhibition by IL-4 in 9 out of 10 cases tested. We conclude that IL-4 inhibits the proliferation of optimally stimulated AML-M4/M 5 cells in most cases tested, and that this effect is not generally ca used by inhibition of autocrine IL-6 production.