title: Differential stimulatory and inhibitory effects of interleukin 4 on granulocytic and monocytic colony formation in human bone marrow cultures.
abstract: Both stimulatory and inhibitory effects of interleukin (IL) 4 on myelopoiesis have been described. In this paper we further define the specificity of these effects. IL-4 was added to cultures of bone marrow cells in which colony formation was stimulated with several colony-stimulating factors (CSFs): monocyte CSF (M-CSF), granulocyte CSF (G-CSF), IL-3, IL-5 and conditioned medium from phytohemagglutinin-stimulated peripheral blood cells (PHA-CM). Inhibition of monocytic colony formation by IL-4 was observed in cultures that were stimulated with IL-3 or with PHA-CM, similar to the inhibition in M-CSF- or GM-CSF-stimulated cultures. The enhancement of granulocytic colony formation by IL-4 was restricted to G-CSF-induced colony growth. No enhancement was observed in cultures that were stimulated with IL-5 or with PHA-CM from which the G-CSF was neutralized by anti-G-CSF antibodies. Both the inhibiting and enhancing effects of IL-4 were preserved in cultures that were stimulated with concentrations of CSF that exceeded more than tenfold the plateau concentrations. Enhancement of granulocytic and inhibition of monocytic colony formation by IL-4 occurred simultaneously in cultures stimulated with PHA-CM or with a combination of G-CSF and M-CSF. In summary, we show that the inhibiting effect of IL-4 on monocytic colony formation is independent of the growth factor used, whereas the stimulatory effect of IL-4 on granulocytic colony formation is restricted to G-CSF-induced cultures. Simultaneous occurrence of both effects results in preferential growth of granulocytes.
authors.affiliation: Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Jansen
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: G J
authors.initials: GJ
authors.lastname: Wientjens
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: J C
authors.initials: JC
authors.lastname: Kluin-Nelemans
mesh_terms: D001853:Bone Marrow / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007377:Interleukin-3; D015848:Interleukin-5; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor