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Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 1967-1972
Interleukin-10 Inhibits Erythropoietin-Independent Growth of
Erythroid Bursts in Patients With Polycythemia Vera
Klaus Geissler,
Leopold Öhler,
Manuela Födinger,
Eva Kabrna,
Marietta Kollars,
Sonja Skoupy, and
Klaus Lechner
From the Division of Hematology of the 1st Medical Department, and
Department of Laboratory Medicine, University of Vienna, Vienna,
Austria.
In polycythemia vera (PV) erythroid colonies that grow in vitro in
the absence of exogenous erythropoietin (EPO) arise from the abnormal
clone that is responsible for overproduction of red blood cells.
Although the mechanism of autonomous formation of burst-forming
units-erythroid (BFU-E) is not fully understood, a spontaneous release
of growth regulatory molecules by PV cells and/or by accessory
cells is likely to be involved. Because of its cytokine synthesis
inhibiting action, interleukin-10 (IL-10) could be a potentially useful
molecule to modulate abnormal erythropoiesis in PV. We studied the
effect of recombinant human IL-10 on the EPO-independent growth of
erythroid bursts derived from peripheral blood mononuclear cells
(PBMNCs) of patients with PV. IL-10 showed a profound, dose-dependent,
and specific inhibitory effect on autonomous BFU-E formation. Ten
nanograms per milliliter of IL-10 significantly suppressed spontaneous
growth of erythroid colonies in methylcellulose in five of five PV
patients tested with a mean inhibition by 81% (range, 72-94). To
elucidate the possible mechanism of the inhibitory action of IL-10 we
further studied the effect of anticytokine antibodies on autonomous
BFU-E growth and the ability of exogenous cytokines to restore
IL-10-induced suppression of erythroid colony growth. Among a panel of
growth regulatory factors tested (granulocyte-macrophage
colony-stimulating factor [GM-CSF], IL-3, granulocyte
colony-stimulating factor, stem cell factor, and insulin-like growth
factor-1) GM-CSF was the only molecule for which both an inhibition of
spontaneous BFU-E formation by its respective antibody as well as a
significant restimulation of erythroid colonies in IL-10-treated
cultures by exogenous addition was found. Moreover, inhibition of
GM-CSF production by IL-10 was shown in PV PBMNCs at the mRNA level.
Our data indicate that autonomous BFU-E growth in PV can be profoundly
inhibited by IL-10 and that this inhibitory effect seems to be at least
in part secondary to suppression of endogenous GM-CSF production.
© 1998 by The American Society of Hematology.
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