Interleukin-1 synergizes with granulocyte-macrophage colony-stimulating
factor on granulocytic colony formation by intermediate production of
granulocyte colony-stimulating factor
MR Schaafsma, JH Falkenburg, N Duinkerken, J Van Damme, BW Altrock, R Willemze and WE Fibbe
Department of Hematology, University Medical Center, Leiden, The
Netherlands.
Interleukin-1 (IL-1) was found to act synergistically with granulocyte-
macrophage colony-stimulating factor (GM-CSF) on granulocytic colony growth
of normal human bone marrow cells, depleted of mononuclear phagocytes and T
lymphocytes. Using CD34/HLA-DR-enriched bone marrow cells we demonstrated
that this activity of IL-1 was not a direct action on hematopoietic
progenitor cells, but an effect of an intermediate factor produced by
residual accessory cells in response to IL-1. Neutralization experiments
using an anti-IL-6 antiserum showed that IL-1-induced IL-6 did not
contribute to the observed synergy. Furthermore, IL-6 by itself had neither
a direct stimulatory effect on CFU-GM colony growth, nor did it act
synergistically with GM-CSF on granulocytic or monocytic colony formation.
Neutralization experiments with an anti-G-CSF monoclonal antibody showed
that IL-1-induced G-CSF production was responsible for the synergy with
GM-CSF. Using combinations of G-CSF and GM-CSF this synergistic activity
could be detected at concentrations of G-CSF as low as 0.1 ng/mL (10 U/mL).
Our results indicate that IL-1, but not IL-6, stimulates the GM-CSF-
dependent proliferation of relatively mature myeloid progenitor cells in
the presence of small numbers of accessory cells.
Volume 74,
Issue 7,
pp. 2398-2404,
11/15/1989
Copyright © 1989 by The American Society of Hematology
