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Human cytomegalovirus increases constitutive production of interleukin- 6
and leukemia inhibitory factor by bone marrow stromal cells
L Lagneaux, A Delforge, R Snoeck, E Bosmans, JF Moreau, JL Taupin, E De Clercq, P Stryckmans and D Bron
Service de Medecine Interne et Laboratoire d'Investigation Clinique Henri
Tagnon, Institut J. Bordet, Brussels, Belgium.
Human cytomegalovirus (CMV) infection is often associated with
myelosuppression and acute inflammatory reaction in immunocompromised
patients. We have previously documented that CMV exposure of bone marrow
(BM) stromal cells reduces the capacity of these cells to support
hematopoiesis because of a decreased production of colony- stimulating
factors. This study examines the potential role of CMV on constitutive and
lipopolysaccharide (LPS)-stimulated production of cytokines involved in
inflammatory reaction, interleukin-6 (IL-6) and leukemia inhibitory factor
(LIF) by BM stromal cells. The release of IL- 6 was already detectable 2
hours post CMV-infection (2.5-fold increase in production) and the
cumulative production of IL-6 after 5 days of infection was 23 +/- 1.2
ng/mL (ninefold increase in production). CMV was also able to induce a
time-dependent production of LIF that was maximal 8 hours after CMV
infection (2.5-fold increase in production). Concomitantly, there was no
detectable release of granulocyte colony- stimulating factor (G-CSF) and
granulocyte-macrophage CSF (GM-CSF) by CMV-infected stromal cells. The
similar IL-6 and LIF production in the presence of polymyxin B ruled out
the possibility that this increase could be caused by contamination of the
viral stock by endotoxin. In addition, ultraviolet-inactivated virus
behaved similarly to live virus and caused the release of IL-6 and LIF.
However, heat-inactivated CMV was unable to induce IL-6 and LIF secretion
by BM stromal cells. The production of IL-6 and LIF was also evaluated
after stimulation by LPS. After 5 days of CMV exposure, the LPS-stimulated
production of IL-6 and LIF was significantly lower than uninfected
controls. This LPS-induced release of cytokine production was found to be
dependent of viral replication. The experiments have shown that CMV is a
potent inducer of IL-6 and LIF with differential effect on constitutive and
LPS- stimulated cytokine production by stromal cells; we suggest that CMV
induction of IL-6 and LIF during the first hours of infection could play a
role in CMV-induced inflammatory reaction. Moreover, our results show that
human CMV can disturb the balanced cytokine network involved in the
regulation of hematopoiesis.
Volume 87,
Issue 1,
pp. 59-66,
01/01/1996
Copyright © 1996 by The American Society of Hematology

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