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 (GM-CSF), anti-IL-1 beta nor anti-tumor necrosis factor alpha (TNF alpha) 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.
Yanagisawa
K
K
First Department of Internal Medicine, School of Medicine, Ehime University, Japan.
Kishimoto
K
K
Horiuchi
T
T
Takada
K
K
Yasukawa
M
M
Fujita
S
S
D000906:Antibodies / Q000494:pharmacology; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests
D000906:Antibodies; D015850:Interleukin-6; D015847:Interleukin-4