Interleukin-6 and other gp130-dependent cytokines selectively inhibit proliferation of macrophage-lineage hemopoietic progenitor cells.
OBJECTIVE
Hemopoiesis is regulated by cytokines with positive or negative effects on proliferation of lineage-committed or multipotent hemopoietic stem cells. We have investigated the roles of interleukin-6 and other gp130-dependent ligands on the proliferation of macrophage-lineage hemopoietic progenitor cells.


METHODS
The responses of human and murine hemopoietic cells to combinations of cytokines involving interleukin-6 or related factors were assessed in short-term culture by clonogenic assay.


RESULTS
Interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor inhibited formation of colonies stimulated by macrophage colony-stimulating factor. These effects were dose dependent and selective for macrophage-lineage precursors. Progenitors from murine peripheral blood were inhibited by 37-93% in cultures containing interleukin-6 (11 experiments; median, 68%). Macrophage progenitors from murine bone marrow were also inhibited by interleukin-6 but were less sensitive (seven experiments; median, 48%). In cultures costimulated with leukemia inhibitory factor, peripheral blood and bone marrow progenitors were inhibited by 82% and 58%, respectively. Ciliary neurotrophic factor inhibited macrophage colonies by 66%. Multilineage bone marrow colony formation was not affected. In cultures of human bone marrow cells stimulated with macrophage colony stimulating factor and stem cell factor, interleukin-6 inhibited colony formation by 51-74%. Bone marrow colonies stimulated by granulocyte-macrophage colony stimulating factor were not inhibited by costimulation with interleukin-6.


CONCLUSIONS
These results suggest a novel mechanism for the negative regulation of macrophage-lineage hemopoietic cells. They also demonstrate new properties of interleukin-6 and certain other gp 130-dependent ligands.
Clutterbuck
R
R
Academic Department of Haematology and Cytogenetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom. robync@icr.ac.uk
Powles
R
R
Millar
J
J
Catovsky
D
D
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology
D020934:Ciliary Neurotrophic Factor; D015850:Interleukin-6; D008222:Lymphokines; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C010598:leukocyte inhibitory factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor