IL-4 stimulates the growth of chronic myelomonocytic leukemia cells (CMMoL) once leukemic transformation has occurred.
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.
Yanagisawa
K
K
First Department of Internal Medicine, School of Medicine, Ehime University, Japan.
Hatta
N
N
Watanabe
I
I
Horiuchi
T
T
Hasegawa
H
H
Fujita
S
S
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007621:Karyotyping; D015477:Leukemia, Myelomonocytic, Chronic / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D016207:Cytokines; D015850:Interleukin-6; D015847:Interleukin-4