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Interleukin-11 inhibits adipogenesis and stimulates myelopoiesis in human
long-term marrow cultures
DC Keller, XX Du, EF Srour, R Hoffman and DA Williams
Herman B Wells Center for Pediatric Research, James Whitcomb Riley Hospital
for Children, Indiana University School of Medicine, Indianapolis
46202-5225.
Interleukin-11 (IL-11) is a bone marrow (BM) stromal-derived growth factor
that has been shown to stimulate murine myeloid and lymphoid cells both in
vitro and in vivo and to inhibit adipogenesis in a murine fibroblast cell
line. We have studied the effects of IL-11 on highly purified human BM stem
and progenitor cells and on human long-term marrow cultures (LTMC).
Adipocyte differentiation is an integral component of murine and human
LTMC. IL-11 stimulates myeloid growth as a single cytokine when added to
highly enriched CD34+, HLA-DR+ bone marrow cells. IL-11 stimulated no
growth in the more primitive CD34+, HLA-DR- population even in the presence
of additional cytokines. IL-11 addition to human LTMC resulted in the
expansion of myeloid and mixed, but not erythroid, progenitor populations.
IL-11 dramatically increased the adherent cell populations, including both
stromal cells and macrophages. Treated cultures also showed marked
inhibition of fat accumulation in the adherent cells due in part to a block
in the differentiation of preadipocytes to adipocytes, as shown by RNA
analysis using adipocyte-specific markers. These data show that IL-11
stimulates a more differentiated, although multipotential, progenitor cell
in human BM and that LTMC provide a useful model for studying the effects
of this cytokine in the context of the hematopoietic microenvironment.
Volume 82,
Issue 5,
pp. 1428-1435,
09/01/1993
Copyright © 1993 by The American Society of Hematology
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