|
|
 Previous Article | Table of Contents | Next Article 
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
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Oehler, E. Jaeger, A. Eser, C. Sillaber, H. Gisslinger, and K. Geissler
Imatinib mesylate inhibits autonomous erythropoiesis in patients with polycythemia vera in vitro
Blood,
September 15, 2003;
102(6):
2240 - 2242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Arceci, B. J. Longley, and P. D. Emanuel
Atypical Cellular Disorders
Hematology,
January 1, 2002;
2002(1):
297 - 314.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S.-i. Hashimoto, I. Komuro, M. Yamada, and K. S. Akagawa
IL-10 Inhibits Granulocyte-Macrophage Colony-Stimulating Factor-Dependent Human Monocyte Survival at the Early Stage of the Culture and Inhibits the Generation of Macrophages
J. Immunol.,
October 1, 2001;
167(7):
3619 - 3625.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-M. O'Farrell, D. A. Parry, F. Zindy, M. F. Roussel, E. Lees, K. W. Moore, and A. L.-F. Mui
Stat3-Dependent Induction of p19INK4D by IL-10 Contributes to Inhibition of Macrophage Proliferation
J. Immunol.,
May 1, 2000;
164(9):
4607 - 4615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. R. Goodman, P. Stricker, M. Velavicius, R. Fonseca, E. Kleinstein, R. Lavery, E. A. Deitch, C. J. Hauser, and H. H. Simms
Role of Granulocyte-Macrophage Colony-Stimulating Factor and Its Receptor in the Genesis of Acute Respiratory Distress Syndrome Through an Effect on Neutrophil Apoptosis
Arch Surg,
October 1, 1999;
134(10):
1049 - 1054.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ochi, W. M. Hirani, Q. Yuan, D. S. Friend, K. F. Austen, and J. A. Boyce
T Helper Cell Type 2 Cytokine-Mediated Comitogenic Responses and Ccr3 Expression during Differentiation of Human Mast Cells in Vitro
J. Exp. Med.,
July 19, 1999;
190(2):
267 - 280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Matsumoto, K. Tateda, S. Miyazaki, N. Furuya, A. Ohno, Y. Ishii, Y. Hirakata, and K. Yamaguchi
Effect of Interleukin-10 on Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice
Antimicrob. Agents Chemother.,
November 1, 1998;
42(11):
2853 - 2857.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Geissler, L. Ohler, M. Fodinger, E. Kabrna, M. Kollars, S. Skoupy, and K. Lechner
Interleukin-10 Inhibits Erythropoietin-Independent Growth of Erythroid Bursts in Patients With Polycythemia Vera
Blood,
September 15, 1998;
92(6):
1967 - 1972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
