Divergent effects of IL-10 and IL-4 on the proliferation and growth factor secretion by acute myeloblastic leukemic cells

The effects of interleukin-10 (IL-10) and IL-4 were studied on the spontaneous and IL-1, IL-3, and Granulocyte-Colony Stimulating Factor (G-CSF) supported proliferation of acute myeloid leukemic cells, IL-10 inhibited the spontaneous proliferation in 1 out of 12 (1/12) cases while the IL-1 stimulated the tritiated thymidine (3H-TdR) uptake was suppressed in 2/12 cases as a result of IL-10 administration, In the presence of G-CSF, IL-10 affected 3H-TdR uptake in 2/12 and no distinct changes were observed in the presence of IL-3. In contrast IL-4 alone stimulated (H-3-TdR) uptake with a factor two or more in 7/12 cases, In the presence of IL-1 and G-CSF a further enhancement was noted in 2 and 5 cases respectively, In 2/12 cases IL-4 inhibited the spontaneous or IL-1 and G-CSF supported proliferation, To study whether the changes in H-3-TdR uptake are related to the endogenous secretion of G-CSF and GM-CSF, AML blast cells (n = 5) were cultured in medium supplemented with IL-1 or IL-3 in the absence and presence of IL-10 and IL-4, IL-10 did not inhibit the spontaneous secretion of G-CSF or GM-CSF but suppressed the IL-1 induced GM-CSF secretion in 2/5 cases. These moderate effects were observed despite the strong inhibition of IL-10 on the IL-6 secretion by human activated monocytes, In contrast to IL-10, IL-4 also inhibited the spontaneous (3/5) and cytokine induced (5/5) secretion of G-CSF and GM-CSF (4/5) protein in the cases in which an enhancement of the H-3-TdR uptake was noticed, In summary the data indicate that the proliferative effects of IL-4 are in some cases uncoupled from the endogenous secretion of cytokines, In addition IL-IO affects the AML cells in a limited number of cases despite the similarity in effects between IL-4 and IL-10 in suppressing cytokine secretion from activated human monocytes