Effect of interleukin 6 on in vitro human megakaryocytopoiesis: its interaction with other cytokines.
The effects of human recombinant interleukin 6 (rIL-6) on in vitro human megakaryocytopoiesis were studied utilizing a serum-depleted culture system. Recombinant IL-6 increased both the number of megakaryocyte (MK) colonies formed and the number of cells comprising individual MK colonies cloned from normal low-density bone marrow (LDBM) cells. This stimulation of MK colony number and size was significantly less than that observed following the addition of recombinant interleukin 3 (rIL-3) or granulocyte-macrophage colony-stimulating factor (rGM-CSF). The addition of either rIL-3 or rGM-CSF, but not rIL-6 promoted MK colony formation by nonadherent, low-density, T-cell-depleted (NALDT-) marrow cells. Recombinant interleukin 1 alpha (rIL-1 alpha) and interleukin 4 (rIL-4) failed either to promote LDBM MK colony formation when added alone or to significantly increase rIL-6-promoted MK colony formation. MK colony formation promoted by optimal doses of rIL-6 was, in fact, significantly inhibited by rIL-1 alpha at all concentrations tested. Addition of either recombinant erythropoietin (rEpo) or purified thrombocytopoiesis-stimulating factor (TSF) to assays containing rIL-6 also resulted in significant inhibition of MK colony formation. The effect of suboptimal concentrations of rIL-6 on MK colony formation was additive to that of rIL-3 but not rGM-CSF. The addition of transforming growth factor beta (TGF-beta) resulted in a 58% reduction of rIL-6-promoted MK colony formation by LDBM. These data suggest that rIL-6 can promote in vitro megakaryocytopoiesis and that this effect can be either augmented or inhibited by the addition of several other cytokines. Recombinant IL-6, however, might affect the MK colony-forming unit (CFU-MK) by acting through bone marrow accessory cells or requiring the presence of as yet unidentified additional cytokines.
Bruno
E
E
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Hoffman
R
R
D001685:Biological Factors / Q000494:pharmacology*; D002469:Cell Separation; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016207:Cytokines; D004347:Drug Interactions; D005455:Fluorescent Antibody Technique; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor