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.