INTERLEUKIN-10 INHIBITS SPONTANEOUS COLONY-FORMING UNIT-GRANULOCYTE-MACROPHAGE GROWTH FROM HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS BY SUPPRESSION OF ENDOGENOUS GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTORRELEASE

Spontaneous growth of myeloid colonies (colony-forming unit-granulocyt e-macrophage [CFU-GM]) can be observed in methylcellulose cultures con taining peripheral blood mononuclear cells (PB-MNCs) and is supposedly caused by the release of colony-stimulating factors (CSF) by accessor y cells. Because of its cytokine synthesis-inhibiting effects on T lym phocytes and monocytes, interleukin-10 (IL-10) may be a potential cand idate for indirect modulation of hematopoiesis. We studied the effect of recombinant human IL-10 (rhlL-10) on spontaneous growth of myeloid colonies derived from human PB-MNCs. A total of 10 ng/mL of IL-10 almo st 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 p revent IL-10-induced expression of CFU-GM growth. Spontaneous CFU-GM g rowth, which required the presence of both monocytes (CD14(+) cells) a nd T lymphocytes (CD3(+) cells), was also greatly suppressed by a neut ralizing anti-granulocyte-macrophage CSF (GM-CSF) antibody but was onl y slightly or not at all inhibited by antibodies against G-CSF or IL-3 . Moreover, IL-10-suppressed colony growth could be completely restore d by the addition of exogenous GM-CSF. Using semiquantitative polymera se chain reaction, we were able to show that GMCSF transcripts that sp ontaneously increased in PB-MNCs within 48 hours of culture were marke dly reduced by the addition of IL-10. Inhibiton of GM-CSF production i n PBMNCs by IL-10 was also confirmed at the protein level by measuring GM-CSF levels in suspension cultures. Our findings suggest that auton omous 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 spontan eous cell growth in vitro, this cytokine may be useful in myeloid mali gnancies in which autocrine and/or paracrine mechanisms involving GM-C SF are likely to play a pathogenetic role. (C) 1997 by The American So ciety of Hematology.