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Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of
leukemic human megakaryoblasts
MA Brach, B Lowenberg, L Mantovani, U Schwulera, R Mertelsmann and F Herrmann
Department of Hematology and Oncology, University of Freiburg, Germany.
We have examined the in vitro effects of recombinant human (rh)
interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained
from patients with acute megakaryoblastic leukemia. We demonstrate that
both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation
of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to
35-fold) and also resulted in colony formation of leukemic megakaryoblasts.
However, the stimulatory effect of IL-1 was dependent on endogenous
production of IL-6, because addition of neutralizing monoclonal antibody
(MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast,
neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF),
granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to
counteract the growth- enhancing effects of IL-1. Leukemic megakaryoblasts
accumulated IL-6 mRNA and released IL-6 protein into their culture
supernatant when exposed to rh IL-1 but failed to disclose transcripts for
G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor
(IL-6R) transcript levels demonstrated that megakaryoblasts constitutively
expressed IL-6R mRNA and that these transcripts are down-regulated to
undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-
thymidine incorporation by megakaryoblasts could be duplicated by exogenous
IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our
results suggest that leukemic megakaryoblasts could produce and secrete
IL-6, and express IL-6R, and that the growth- enhancing effect of IL-1 on
these cells is indirect, via production of IL-6 by leukemic cells.
Volume 76,
Issue 10,
pp. 1972-1979,
11/15/1990
Copyright © 1990 by The American Society of Hematology
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