title: Interleukin-10 inhibits erythropoietin-independent growth of erythroid bursts in patients with polycythemia vera.
abstract: 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.
authors.affiliation: Division of Hematology of the 1st Medical Department, and Department of Laboratory Medicine, University of Vienna, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Geissler
authors.forename: L
authors.initials: L
authors.lastname: Ohler
authors.forename: M
authors.initials: M
authors.lastname: Födinger
authors.forename: E
authors.initials: E
authors.lastname: Kabrna
authors.forename: M
authors.initials: M
authors.lastname: Kollars
authors.forename: S
authors.initials: S
authors.lastname: Skoupy
authors.forename: K
authors.initials: K
authors.lastname: Lechner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000473:pathology; D004921:Erythropoietin / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000097:blood*
chemical_list: D006131:Growth Inhibitors; D006133:Growth Substances; D007106:Immune Sera; D004921:Erythropoietin; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor