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Interleukin-10 inhibits spontaneous colony-forming unit-granulocyte-
macrophage growth from human peripheral blood mononuclear cells by
suppression of endogenous granulocyte-macrophage colony-stimulating factor
release
L Oehler, M Foedinger, M Koeller, M Kollars, E Reiter, B Bohle, S Skoupy, G Fritsch, K Lechner and K Geissler
Department of Laboratory Medicine, University of Vienna, St Anna Children's
Cancer Research Institute, Austria.
Spontaneous growth of myeloid colonies (colony-forming unit-granulocyte-
macrophage [CFU-GM]) can be observed in methylcellulose cultures containing
peripheral blood mononuclear cells (PB-MNCs) and is supposedly caused by
the release of colony-stimulating factors (CSF) by accessory cells. Because
of its cytokine synthesis-inhibiting effects on T lymphocytes and
monocytes, interleukin-10 (IL-10) may be a potential candidate for indirect
modulation of hematopoiesis. We studied the effect of recombinant human
IL-10 (rhIL-10) on spontaneous growth of myeloid colonies derived from
human PB-MNCs. A total of 10 ng/mL of IL-10 almost completely inhibited
spontaneous CFU-GM proliferation (by 95.1%; P < .001, n = 7) in
unseparated PB-MNCs. This effect was dose-dependent and specific, because a
neutralizing anti-IL- 10 antibody was able to prevent IL-10-induced
suppression of CFU-GM growth. Spontaneous CFU-GM growth, which required the
presence of both monocytes (CD14+ cells) and T lymphocytes (CD3+ cells),
was also greatly suppressed by a neutralizing anti-granulocyte-macrophage
CSF (GM-CSF) antibody but was only slightly or not at all inhibited by
antibodies against G-CSF or IL-3. Moreover, IL-10-suppressed colony growth
could be completely restored by the addition of exogenous GM- CSF. Using
semiquantitative polymerase chain reaction, we were able to show that
GM-CSF transcripts that spontaneously increased in PB-MNCs within 48 hours
of culture were markedly reduced by the addition of IL- 10. Inhibiton of
GM-CSF production in PB-MNCs by IL-10 was also confirmed at the protein
level by measuring GM-CSF levels in suspension cultures. Our findings
suggest that autonomous CFU-GM growth, resulting from an interaction of
monocytes and T lymphocytes, is mainly caused by endogenous GM-CSF release
and can be profoundly suppressed by the addition of exogenous IL-10.
Considering the strong inhibitory action of IL-10 on GM-CSF production and
spontaneous cell growth in vitro, this cytokine may be useful in myeloid
malignancies in which autocrine and/or paracrine mechanisms involving
GM-CSF are likely to play a pathogenetic role.
Volume 89,
Issue 4,
pp. 1147-1153,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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