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Constitutive in vivo cytokine and hematopoietic growth factor gene
expression in the bone marrow and peripheral blood of healthy individuals
FH Cluitmans, BH Esendam, JE Landegent, R Willemze and JH Falkenburg
Department of Hematology, University Medical Center, Leiden, The
Netherlands.
We investigated hematopoietic growth factor (HGF) and cytokine gene
expression in the bone marrow (BM) and peripheral blood (PB) of healthy
individuals as a starting point for delineating the physiologic role of
cytokines in steady state hematopoiesis. BM biopsy specimens and PB samples
from 7 healthy individuals were analyzed by polymerase chain reaction
amplification of reverse-transcribed RNA using gene-specific primer sets.
Consistent gene expression in the BM of all 7 individuals was detected for
macrophage colony-stimulating factor (CSF), stem cell factor, interleukin-6
(IL-6), IL-7, erythroid-potentiating factor, erythroid-differentiating
factor, and insulinlike growth factor 1, all cytokines with reported direct
stimulatory effects on in vitro hematopoiesis. Of these,
erythroid-potentiating factor and erythroid- differentiating factor
appeared to be the only stimulating factors that were also expressed in the
PB. Among the cytokines with inhibitory effects on in vitro hematopoiesis
IL-4, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, transforming
growth factor-beta, and macrophage inflammatory protein-1 alpha were
expressed in the BM of the 7 individuals. Except for TNF-alpha, the latter
cytokines were also expressed in the PB. Consistent expression in the BM
and PB of all tested individuals was also observed for IL-1 beta, IL-1
receptor antagonist, and IL-1 beta converting enzyme, which are all members
of the IL-1 family with a possible indirect effect on hematopoiesis.
Remarkably, no expression of granulocyte CSF, granulocyte-macrophage CSF,
and IL-3 was found in the BM or PB of all investigated individuals (n =
15). This was also the case for IL-1 alpha, IL-2, IL-5, IL-9, IL- 12,
IL-13, leukemia-inhibiting factor, interferon-gamma, and inhibin. Weak IL-8
and IL-10 expression was found in the BM and/or PB of a minority of
investigated individuals. These findings provide insight into which
cytokines or HGFs potentially are involved in the autocrine or paracrine
regulation of in vivo steady state hematopoiesis. The absence of expression
of granulocyte CSF, granulocyte-macrophage CSF, and IL-3 in the BM of
healthy individuals implicates that it is highly unlikely that these HGFs
are involved in the autocrine or paracrine regulation of constitutive
hematopoiesis.
Volume 85,
Issue 8,
pp. 2038-2044,
04/15/1995
Copyright © 1995 by The American Society of Hematology
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