Antagonistic effects of interleukin 6 and G-CSF in the later stage of human granulopoiesis in vitro.
The effect of recombinant human interleukin 6 (rhIL-6) on the in vitro growth of human bone marrow myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) was investigated. Recombinant human IL-6 by itself did not induce colony formation. When rhIL-6 at various concentrations was added to the CFU-GM colony cultures containing recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-monocyte/macrophage colony-stimulating factor (rhGM-CSF), rhIL-6 significantly suppressed the colony formation induced by rhG-CSF, but not by rhGM-CSF. This suppressive effect of rhIL-6 on rhG-CSF-induced, but not rhGM-CSF-induced colony formation was confirmed by using an MY10(+)-cell-enriched population. Neither interleukin 3 nor interleukin 1 alpha suppressed the growth of myeloid progenitors. The preincubation of bone marrow cells with rhIL-6 for a short time (30 min) resulted in a reduction of colonies induced by rhG-CSF, but not by rhGM-CSF. The suppressive effect of rhIL-6 on rhG-CSF-induced colony formation was not observed when the cells were preincubated together with rhG-CSF at a high ratio of rhG-CSF to rhIL-6. The rhIL-6-mediated suppressive effect was further confirmed by blocking the effect by the anti-IL-6 antibody. These results suggest antagonistic interaction between IL-6 and G-CSF in the later differentiation of myeloid progenitors.
Katayama
K
K
Department of Pediatrics, Kanazawa University School of Medicine, Japan.
Koizumi
S
S
Ueno
Y
Y
Ohno
I
I
Ichihara
T
T
Horita
S
S
Miyawaki
T
T
Taniguchi
N
N
D000328:Adult; D001854:Bone Marrow Cells; D002455:Cell Division; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004347:Drug Interactions; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000166:cytology*; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D015850:Interleukin-6; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor