Differential stimulatory and inhibitory effects of interleukin 4 on granulocytic and monocytic colony formation in human bone marrow cultures

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Abstract
Both stimulatory and inhibitory effects of interleukin (IL) 4 on myelo‐poiesis have been described. In this paper we further define the specificity of these effects. EL‐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 DL‐4 was observed in cultures that were stimulated with EL‐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.