Actions and interactions of G-CSF, LIF, and IL-6 on normal and leukemic murine cells.
Purified recombinant granulocyte colony stimulating factor (G-CSF) and interleukin-6 (IL-6) stimulated the formation of similar numbers of colonies in cultures of normal mouse marrow cells. LIF and IL-6 induced comparable differentiation in clonal cultures of murine M1 leukemic cells and exhibited enhanced actions in combination. However, LIF was 16-25-fold more active than IL-6. Induction of differentiation in M1 leukemic colonies by both LIF and IL-6 was enhanced by the addition of G-CSF or M-CSF but not by GM-CSF or Multi-CSF. Both G-CSF and IL-6, but not LIF, were able to induce differentiation in murine WEHI-3B leukemic colonies, but G-CSF was 10-fold more efficient than IL-6. Both G-CSF and IL-6 were able to stimulate the proliferation of cells of the NFS-60 continuous cell line, but G-CSF was 30-fold more efficient. M1 cells constitutively produced low levels of IL-6 and production was enhanced by LIF, but the general characteristics of the actions of LIF, IL-6, and G-CSF suggested that each operates independently as a direct differentiation inducer of leukemic cells. The similarities in the biology and actions of G-CSF, LIF, and IL-6 suggest that they may be designed to exhibit coordinated biological functions in certain situations.
Metcalf
D
D
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006131:Growth Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D007942:Leukemia, Experimental / Q000473:pathology*; D008222:Lymphokines; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010954:Plasmacytoma / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D015850:Interleukin-6; D007378:Interleukins; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D016179:Granulocyte Colony-Stimulating Factor