Interleukin-4 in chronic myelomonocytic leukemia: Growth suppression of hematopoietic precursors in the chronic phase and stimulation in the acute phase

We examined the effects of interleukin-4 (IL-4) on the growth of hematopoietic precursors from a patient with chronic myelomonocytic leukemia (CMMoL). In the chronic phase of the disease, IL-4 inhibited spontaneous colony formation by CMMoL cells in semi-solid culture. However, in the acute phase, IL-4 promoted colony formation. These effects of IL-4 were abolished completely by the addition of anti-IL-4 neutralizing antibodies. The spontaneous colony formation by CMMoL cells in both the chronic and acute phases was inhibited by the addition of anti-IL-6 antibodies. On the other hand, neither anti-IL-6, anti-granulocyte macrophage colony-stimulating factor (GMCSF), anti-IL-1β nor anti-tumor necrosis factor α (TNFα) antibodies inhibited IL-4-induced colony formation by CMMoL cells in the acute phase. IL-4 suppressed the production of IL-6 by CMMoL cells in both the chronic and acute phases. These results suggest that in the present patient, IL-4 suppressed the IL-6-mediated autocrine growth of CMMoL cells in both the chronic and acute phases, but directly stimulated their growth in the acute phase.