Yanagisawa K, Hatta N, Watanabe I, Horiuchi T, Hasegawa H, Fujita S
First Department of Internal Medicine, School of Medicine, Ehime University, Japan.
Leukemia. 1995 Jun;9(6):1056-9.
We have investigated the effects of interleukin-4 (IL-4) on the proliferation of chronic myelomonocytic leukemia (CMMoL) cells in the chronic and leukemic transformation phases in vitro. CMMoL cells formed colonies spontaneously in both phases. IL-4 suppressed the spontaneous growth in the chronic phase, but on the other hand, stimulated colony formation in the leukemic transformation phase. Anti-IL-6 antibody inhibited spontaneous colony formation in both phases. CMMoL cells in both phases produced high levels of IL-6, compared with those produced by acute myelogenous leukemia (AML) cells showing myelomonocytic differentiation and normal monocytes. IL-4 suppressed the IL-6 production by CMMoL cells in both phases. None of anti-IL-6, anti-macrophage colony-stimulating factor (M-CSF), anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-tumor necrosis factor-alpha (TNF-alpha) and anti-IL-1-beta antibodies inhibited IL-4-stimulated colony formation. These results suggest that IL-4 directly stimulates the growth of CMMoL cells once leukemic transformation has occurred and that the therapeutic use of IL-4 for CMMoL should be viewed with caution, especially in the leukemic transformation phase.
我们已经在体外研究了白细胞介素-4（IL-4）对慢性粒单核细胞白血病（CMMoL）细胞在慢性期和白血病转化期增殖的影响。CMMoL细胞在两个阶段均能自发形成集落。IL-4在慢性期抑制自发生长，但另一方面，在白血病转化期刺激集落形成。抗IL-6抗体在两个阶段均抑制自发集落形成。与显示粒单核细胞分化的急性髓性白血病（AML）细胞和正常单核细胞产生的IL-6相比，两个阶段的CMMoL细胞均产生高水平的IL-6。IL-4在两个阶段均抑制CMMoL细胞产生IL-6。抗IL-6、抗巨噬细胞集落刺激因子（M-CSF）、抗粒细胞巨噬细胞集落刺激因子（GM-CSF）、抗肿瘤坏死因子-α（TNF-α）和抗IL-1-β抗体均未抑制IL-4刺激的集落形成。这些结果表明，一旦发生白血病转化，IL-4可直接刺激CMMoL细胞生长，并且对于CMMoL，应谨慎看待IL-4的治疗用途，尤其是在白血病转化期。
