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  • Title: In vitro differentiation and proliferation of human hematopoietic progenitors: the effects of interleukins 1 and 6 are indirectly mediated by production of granulocyte-macrophage colony-stimulating factor and interleukin 3.
    Author: Migliaccio G, Migliaccio AR, Adamson JW.
    Journal: Exp Hematol; 1991 Jan; 19(1):3-10. PubMed ID: 1989893.
    Abstract:
    The effect of recombinant human interleukin (IL)-1 and IL-6 on the differentiation and proliferation in vitro of human granulocyte-macrophage (GM) and erythroid progenitors has been investigated in either fetal bovine serum (FBS)-supplemented or FBS-deprived cultures. Sources of progenitor cells were unfractionated bone marrow cells or marrow cells depleted of adherent and/or T cells. Each interleukin was investigated either alone or in combination with GM-colony-stimulating factor (CSF), IL-3 and erythropoietin (Epo), or granulocyte (G)-CSF. In FBS-supplemented cultures of unfractionated marrow cells, IL-1 induced optimal GM colony growth and increased by 50% the number of erythroid bursts that formed in the presence of Epo. The addition to these cultures of a neutralizing anti-GM-CSF monoclonal antibody or of an anti-IL-3 serum decreased the growth of GM colonies by 80% and 40%, respectively. Under the same conditions, IL-6 had no effect on GM colony growth but increased by 90% the number of erythroid bursts. This effect was partially (40%) neutralized by addition of anti-IL-3 serum. IL-1 and IL-6 were weak stimuli, or had no effect at all, either alone or in combination with GM-CSF and IL-3 in FBS-deprived cultures or in FBS-supplemented cultures of nonadherent or nonadherent, T-cell-depleted marrow cells. IL-1 and IL-6 had no effect, either alone or in combination with IL-3, in maintaining the number of progenitor cells in short-term liquid suspension cultures. These results indicate that the actions of IL-1 and IL-6 on hematopoiesis are mainly indirect and mediated by the production of GM-CSF and/or IL-3 by accessory cells. However, neither IL-1 nor IL-6 alone is sufficient to stimulate production of growth factor(s) by accessory cells, and at least a second stimulus, provided by FBS, is also required. These data are in agreement with a multisignal model of regulation of the expression of growth factor genes.
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