Mechanism of action of interleukin 1 on the progenitors of blast cells in acute myeloblastic leukemia.
We tested the effect of interleukin 1 (IL-1) on the growth of leukemic blast progenitors from patients with acute myeloblastic leukemia (AML). A purified blast cell fraction depleted of both T cells and phagocytic cells was tested at different cell densities. Addition of 1 ng/ml of IL-1 alpha alone enhanced blast colony formation in 10 of 13 cases tested, and the enhancement was prominent when plated cell densities were lowered. The conditioned media (CM) from AML patients contained varied levels of IL-1 activity, and following depletion of phagocytic cells, the levels decreased markedly in all cases tested. Addition of either antiserum against IL-1 alpha or IL-1 beta reduced the IL-1 activity in CM, suggesting that AML blasts produce both IL-1 alpha and IL-1 beta. Addition of IL-1 alpha or IL-1 beta antiserum inhibited blast colony formation in a dose-dependent manner, and a combination of both antisera showed the most marked inhibition. However, the augmentation of blast colony formation was almost completely inhibited by addition of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) serum in all three cases tested. IL-1 is also devoid of this activity when tested in the presence of a combination of granulocyte CSF (G-CSF), GM-CSF, and interleukin 3 (IL-3) at an optimal concentration. These results suggest that blast cells could produce and secrete CSF(s) and/or IL-1, and that the growth-enhancing effect of IL-1 on AML blasts is indirect, via production of CSFs by leukemic cells.
Murohashi
I
I
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Tohda
S
S
Suzuki
T
T
Nagata
K
K
Yamashita
Y
Y
Nara
N
N
D003115:Colony-Stimulating Factors / Q000276:immunology / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000276:immunology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007106:Immune Sera; D007375:Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor