Effect of interleukin-11 on cycling status and clonogenic maturation of fetal and adult hematopoietic progenitors.
A recently cloned human cytokine, interleukin-11 (IL-11), has functional similarities to IL-6. We tested the hypothesis that the hematopoietic actions of IL-11 in vitro also resemble those of IL-6. The effect of IL-11 on the cell cycle status of fetal and adult hematopoietic progenitors was assessed using serum-free incubations followed by tritiated thymidine suicide studies. Its effect on clonogenic maturation was assessed by including IL-11, either as a single agent or with subplateau or plateau concentrations of other recombinant cytokines, in cultures that contained neutralizing monoclonal antibodies directed against relevant growth factors. Similar to IL-6, IL-11 resulted in accelerated cycling of fetal colony-forming units-mixed (CFU-MIX), CFU-granulocyte macrophage (CFU-GM), and erythroid burst-forming units (BFU-E). This effect was additive to that of submaximal, but not to plateau, concentrations of IL-6. However, no effect of IL-11 was observed on cycling status of adult progenitors. As a single agent, IL-11 failed to support clonal maturation of either fetal or adult progenitors. IL-11 was additive to GM-CSF in supporting clonal maturation of CFU-GM from adult marrow but not from fetal blood. We conclude that the in vitro hematopoietic actions of IL-11 on cell cycle status of hematopoietic progenitors resemble those of IL-6. However, unlike IL-6, IL-11 as a single agent failed to support clonal maturation of fetal CFU-GM, BFU-E, and CFU-MIX.
Schibler
K R
KR
Division of Human Development and Aging, University of Utah, School of Medicine, Salt Lake City 84132.
Yang
Y C
YC
Christensen
R D
RD
D000328:Adult; D001854:Bone Marrow Cells; D002453:Cell Cycle; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology; D004357:Drug Synergism; D005312:Fetal Blood / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D017370:Interleukin-11; D015850:Interleukin-6 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D011994:Recombinant Proteins / Q000494:pharmacology
D017370:Interleukin-11; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor