Interleukin 4 suppresses the spontaneous growth of chronic myelomonocytic leukemia cells.
We studied the effects of IL-4 on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro. IL-4 (100 U/ml) suppressed the spontaneous DNA synthesis by approximately 50% in 5 of 8 cases examined. IL-4 (100 U/ml) also inhibited the spontaneous colony formation by CMMoL cells in a methylcellulose culture by 50-97% in all of the 10 cases in which spontaneous colonies were formed. This IL-4-mediated suppression of the growth of CMMoL cells was completely abolished by the addition of anti-IL-4 neutralizing antibodies. The spontaneous CMMoL colonies were substantially suppressed by the addition of either anti-IL-6 or anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies to the colony assay system: the addition of both anti-IL-6 and anti-GM-CSF antibodies resulted in greater than 80% inhibition of the colony formation by CMMoL cells. On the other hand, none of anti-IL-1-beta, anti-granulocyte-CSF, anti-macrophage-CSF, or anti-tumor necrosis factor-alpha antibodies affected the CMMoL colony formation. In the supernatants from 24-h cultures of CMMoL cells, high levels of IL-6 and GM-CSF were demonstrated in 9 of 9 and 2 of 9 cases examined, respectively. IL-4 (100 U/ml) almost completely inhibited the secretion of IL-6 and GM-CSF by CMMoL cells. These observations suggest that IL-4 suppresses the spontaneous proliferation of CMMoL cells by inhibiting their production of IL-6 and/or GM-CSF, both of which could act in vitro as an autocrine growth factor for CMMoL cells.
Akashi
K
K
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Shibuya
T
T
Harada
M
M
Takamatsu
Y
Y
Uike
N
N
Eto
T
T
Niho
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011817:Rabbits
D015850:Interleukin-6; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA