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Synergism between interleukin-6 and interleukin-3 in supporting
proliferation of human hematopoietic stem cells: comparison with
interleukin-1 alpha
AG Leary, K Ikebuchi, Y Hirai, GG Wong, YC Yang, SC Clark and M Ogawa
VA Medical Center, Charleston, SC.
Currently available evidence suggests that in the steady state, the
majority of hematopoietic stem cells are dormant in cell cycle and reside
in the so-called G0 period. Studies in our laboratory indicated that once a
stem cell leaves G0, its subsequent proliferation requires the presence of
interleukin-3 (IL-3). Recently it was reported that interleukin-1 (IL-1)
may stimulate stem cells to become sensitive to IL- 3. In a separate study,
we observed that interleukin-6 (IL-6, also known as B cell stimulatory
factor-2/interferon beta 2) possesses synergism with IL-3, shortening the
G0 period of murine hematopoietic stem cells. We report here that human
IL-6 and IL-3 act synergistically in support of the proliferation of
progenitors for human blast cell colonies and that IL-1 alpha reveals no
synergism with IL-3 when tested against purified human marrow progenitors.
Panned My-10+ human marrow cells were plated in culture and on day 14 of
incubation, either IL-3, IL-6, IL-1 alpha or a combination of these factors
was added to the cultures. Blast cell colony formation was analyzed daily
between days 18 and 32 of culture. IL-6 or IL-1 alpha alone failed to
support blast cell colony formation. In the presence of IL-3 alone, blast
cell colonies continued to emerge between days 21 and 27. When a
combination of IL-3 and IL-6 was added, blast cell colonies developed
earlier than in cultures with IL-3 alone and twice as many blast cell
colonies were identified. IL-1 alpha failed to augment IL-3-dependent blast
cell colony formation. Replating studies of the individual blast cell
colonies revealed various types of single as well as multilineage colonies.
These observations suggest that IL-6 shortens the G0 period of human
hematopoietic stem cells and that the reported synergistic activities of
IL-1 on primitive hematopoietic cells may be indirect.
Volume 71,
Issue 6,
pp. 1759-1763,
06/01/1988
Copyright © 1988 by The American Society of Hematology
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