In vivo and in vitro interaction between interleukin 6 and granulocyte colony-stimulating factor in the regulation of murine hematopoiesis.
The interaction both in vitro and in vivo between human recombinant interleukin 6 (IL-6) and human recombinant granulocyte colony-stimulating factor (G-CSF) in the regulation of mouse hematopoiesis was investigated. In the in vitro experiments, mouse bone marrow and spleen cells were cultured in semisolid medium containing 5 or 50 ng/ml of G-CSF and concentrations ranging from 0 to 20 ng/ml of IL-6. In vivo, mice were treated for 4 days with 15, 50, or 250 micrograms/kg body weight/day of G-CSF, or with similar doses of G-CSF plus 50 micrograms/kg/day of IL-6, and the numbers of stem (spleen colony-forming units, CFU-S) and progenitor (megakaryocyte colony-forming cells, Meg-CFC; granulocyte-macrophage colony-forming cells, GM-CFC) hematopoietic cells and mature circulating blood cells were evaluated. In vitro IL-6 caused dose-dependent suppression of the proliferation of GM-CFC, decreasing numbers of granulocyte-macrophage colonies in culture. The inhibitory effect of IL-6 decreased along with the increase of density of cultured cells, suggesting the influence of accessory, cytokine-producing cells. In vivo, the numbers of GM-CFC and Meg-CFC in mice treated with IL-6 plus G-CSF were significantly closer to the values observed in untreated animals than those in mice treated with G-CSF only. The other cell populations were unaffected by IL-6 treatment. Our results demonstrate antagonism between IL-6 and G-CSF in the in vitro stimulation of the proliferation of late granulocyte precursors, and they suggest a similar effect in the in vivo regulation of granulopoiesis and megakaryocytopoiesis at the progenitor cell level.
Pojda
Z
Z
Division of Radiation Hazards, National Institute of Radiological Sciences, Chiba, Japan.
Tanaka
K
K
Aoki
Y
Y
Tsuboi
A
A
D000818:Animals; D001854:Bone Marrow Cells; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D013154:Spleen / Q000166:cytology
D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor