International Journal of Cell Cloning, Vol 9, 570-578, Copyright © 1991 by AlphaMed Press
Differential stimulatory and inhibitory effects of interleukin 4 on granulocytic and monocytic colony formation in human bone marrow cultures
JH Jansen, WE Fibbe, GJ Wientjens, R Willemze and JC Kluin-Nelemans
Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, The Netherlands.
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.
