title: Direct synergistic effects of IL-4 and IL-11 on proliferation of primitive hematopoietic progenitor cells.
abstract: The present studies have investigated, for the first time, the synergistic effects of interleukin-4 (IL-4) and IL-11 on the growth of single murine bone marrow progenitor cells. These studies suggest that IL-4 and IL-11 are synergistic hematopoietic growth factors, enhancing colony formation of bone marrow progenitors from normal mice in the presence of colony-stimulating factors or stem cell factor, whereas neither IL-4 nor IL-11, alone or in combination, resulted in colony formation. However, in the presence of a neutralizing anti-TGF-beta antibody, IL-11 plus IL-4 induced clonal growth of primitive Lin-Sca1+ progenitors. Furthermore, here we report several observations extending the knowledge about IL-4 and IL-11 as synergistic factors. In addition to the established ability of IL-11 to enhance IL-3- and GM-CSF-induced colony formation, IL-11 also enhanced the number of G-CSF- and CSF-1-stimulated colonies of mature (Lin-) and primitive (Lin-Sca-1+) hematopoietic progenitors cultured at the single-cell level. In contrast, IL-4 bifunctionally regulated the growth of Lin- progenitors, whereas the growth of single Lin-Sca=1+ progenitors was unaffected or enhanced in the presence of IL-4. Finally, IL-4 and IL-11, in combination, potently synergized to enhance the high-proliferative-potential colony-forming cell colony formation of Lin-Sca-1+ progenitors in response to all four CSFs and to SCF.
authors.affiliation: Department of Immunology, Norwegian Radium Hospital, Oslo.
authors.forename: F W
authors.initials: FW
authors.lastname: Jacobsen
authors.forename: J R
authors.initials: JR
authors.lastname: Keller
authors.forename: F W
authors.initials: FW
authors.lastname: Ruscetti
authors.forename: O P
authors.initials: OP
authors.lastname: Veiby
authors.forename: S E
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology
chemical_list: D000906:Antibodies; D017370:Interleukin-11; D007377:Interleukin-3; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor