Interleukin-10 inhibits burst-forming unit erythroid growth by suppressionof endogenous granulocyte-macrophage colony-stimulating factor production from T cells

Numerous cytokines released from accessory cells have been shown to exert e ither stimulatory or inhibitory growth signals on burst-forming unit-erythr oid (BFU-E) growth. Because of its cytokine synthesis-inhibiting effects on T cells and monocytes, interleukin-10 (IL-10) may be a potential candidate for indirectly affecting erythropoiesis. We investigated the effects of IL -10 on BFU-E growth from normal human peripheral blood mononuclear cells (P BMC) using a clonogenic progenitor cell assay. The addition of recombinant human IL-10 to cultures containing recombinant human erythropoietin suppres sed BFU-E growth in a dose-dependent manner (by 55.2%, range 47.3-63.3%,p < 0.01, at 10 ng/mL), In contrast, no inhibitory effect of IL-10 was seen wh en cultivating highly enriched CD34(+) cells. BFU-E growth from PBMC also w as markedly suppressed in the presence of a neutralizing anti-granulocyte-m acrophage colony-stimulating factor (GM-CSF) antibody (by 48.7%, range 32.9 -61.2% inhibition,p < 0.01), but not by neutralizing antibodies against gra nulocyte colony-stimulating factor and interleukin-3, This suggests a stimu latory role of endogenously released GM-CSF on BFU-E formation. Also, the a ddition of exogenous GM-CSF completely restored IL-10-induced suppression o f BFU-E growth. To determine the cellular source of GM-CSF production, we a nalyzed GM-CSF levels in suspension cultures containing PBMC that were eith er depleted of monocytes or T cells. Monocyte-depleted PBMC showed spontane ous production of increasing amounts of GMCSF on days 3, 5, and 7, respecti vely, which could be suppressed by IL-10, whereas GM-CSP levels did not inc rease in cultures containing T-cell-depleted PBMC, Our data indicate that I L-10 inhibits the growth of erythroid progenitor cells in vitro, most likel y by suppression of endogenous GM-CSF production from T cells. (C) 1999 Int ernational Society for Experimental Hematology. Published by Elsevier Scien ce Inc.