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Human interleukin-6 supports granulocytic differentiation of hematopoietic
progenitor cells and acts synergistically with GM-CSF
D Caracciolo, SC Clark and G Rovera
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Recombinant human (rh) interleukin-6 (IL-6), in a dose range of 1 to 10
U/mL, was able to induce a low number of neutrophilic-granulocytic colonies
in a CFU-GM clonogenic assay, using T cells and adherent cells, depleted
low density marrow cells. A synergistic increase in the number of
granulocytic colonies was observed when rhGM-CSF at suboptimal doses and
IL-6 at effective doses were both present in the assay; the increase was
only additive when either rhIL-1 alpha or rhIL- 3 was used together with
IL-6. To determine whether the increase in colony number reflects the
interactions of these factors on the same hematopoietic progenitor target
cells or, instead, represents activation of accessory cells, we analyzed
the effect of IL-6 on the proliferation and differentiation of three growth
factor-dependent leukemic cell lines that respond with continuous
proliferation to the presence of GM-CSF and IL-3 in culture. One of the
three cell lines (AML-193) showed limited proliferation in the presence of
IL-6 followed by terminal differentiation after 14 days into
basophilic-granulocytic- like cells. A synergistic proliferative response
was observed on the same cells treated with both GM-CSF and IL-6. These
data support the hypothesis that IL-6 may have a direct effect on myeloid
hematopoietic progenitor cells, and that GM-CSF interacts synergistically
with IL-6 by acting on the same target cells.
Volume 73,
Issue 3,
pp. 666-670,
02/15/1989
Copyright © 1989 by The American Society of Hematology
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