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Coordinate secretion of interleukin-1 beta and granulocyte-macrophage
colony-stimulating factor by the blast cells of acute myeloblastic
leukemia: role of interleukin-1 as an endogenous inducer
JC Rodriguez-Cimadevilla, V Beauchemin, L Villeneuve, F Letendre, A Shaw and T Hoang
Clinical Research Institute of Montreal, Hotel-Dieu Hospital, Montreal,
Quebec, Canada.
Acute myeloblastic leukemia (AML) blasts have been shown to produce a
variety of cytokines in culture such as interleukin-1 (IL-1), IL-6,
granulocyte-, macrophage-, and granulocyte-macrophage colony- stimulating
factor (GM-CSF), and tumor necrosis factor-alpha (TNF alpha). Using two
sensitive and specific enzyme-linked immunosorbent assays for IL-1 beta and
GM-CSF, we document in the present study that the production of the two
cytokines by AML blasts in culture is coordinated. First, we observe a
striking correlation between the levels of GM-CSF and IL-1 beta released by
the cells. Thus, a high production of IL-1 beta is always concordant with a
high production of GM-CSF and, conversely, low production of IL-1 beta is
concordant with low levels of GM-CSF. Second, neutralization of intrinsic
IL-1 using antibodies that are specific for IL-1 alpha and -1 beta
suppresses the release of GM-CSF by the cells. Third, neutralization of the
endogenous source of IL-1 also results in an abrogation of GM-CSF mRNA.
Fourth, the production of both IL-1 beta and GM-CSF is up-regulated by
exposing AML blasts to an exogenous source of IL-1, suggesting a positive
regulation of autocrine growth factor production. Taken together, our
results indicate that GM-CSF production by AML blasts is mediated by
endogenously produced IL-1. Both IL-1 beta and -1 alpha are produced by AML
blasts, although IL-1 beta appears to be more abundant. Spontaneous colony
formation by AML blasts is abrogated by the addition of neutralizing
antibodies against IL-1 beta and GM-CSF, whereas each antibody alone has
little effect on blast proliferation. Taken together, our results are
consistent with the view that the production of IL-1 beta by AML blasts
supports autocrine growth in culture, through induction of CSFs or other
cytokines that stimulate blast proliferation.
Volume 76,
Issue 8,
pp. 1481-1489,
10/15/1990
Copyright © 1990 by The American Society of Hematology
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