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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2269-2274
Pharmacologic doses of granulocyte colony-stimulating factor
affect cytokine production by lymphocytes in vitro and in vivo
Elaine M. Sloand,
Sonnie Kim,
Jaroslaw
P. Maciejewski,
Fritz Van Rhee,
Aniruddho Chaudhuri,
John Barrett, and
Neal S. Young
From the National Heart, Lung and Blood Institute, National
Institutes of Health (NIH), Bethesda, MD.
Peripheral blood stem cell (PBSC) transplantation is successful in
improving engraftment without increasing acute graft-versus-host disease (GVHD), despite much larger numbers of T cells in unmanipulated PBSCs than in bone marrow grafts. In mouse models and retrospective human studies, granulocyte colony-stimulating factor (G-CSF) therapy has been associated with less acute GVHD. We studied the effect of
G-CSF on interferon (IFN)- and IL-4 expression in CD4+
lymphocytes. CD4+ cells co-cultivated with G-CSF and
stimulated with PHA or CD3 monoclonal antibodies showed significant
decreases in IFN- and increases in IL-4 expression (n = 13;
P < .01). G-CSF appeared to have a direct effect on
CD4+ cells independent of monocytes present in the
culture because purified CD4+ cells exposed to G-CSF,
washed, and cocultivated with untreated monocytes demonstrated similar
changes in IFN- and IL-4 expression, whereas untreated
CD4+ cells cocultured with G-CSF-stimulated monocytes
behaved as controls. We then studied peripheral blood mononuclear cells
(PBMCs) from G-CSF-mobilized PBSC donors. When their
PBMCs were cultured with PHA or CD3 monoclonal antibody, the
percent of IFN--expressing cells decreased by a mean of 55% and
42%, respectively, whereas the percent of IL-4-containing cells
increased by a mean of 39% and 58%, respectively, following G-CSF
stimulation. Increased apoptosis of IFN--producing
CD4+ cells was not responsible for the shift in TH1/TH2
subsets. G-CSF-R mRNA was present in both CD4+ and
CD8+ cells. These results suggest that G-CSF decreases
IFN- and increases IL-4 production in vitro and in vivo and likely
modulates a balance between TH1 and TH2 cells, an effect that may be
important in PBSC transplantation.
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Modulation of Th1/Th2 subsets by granulocyte-colony stimulating factor
- Muttuswamy Sivakumaran, Zilton F. M. Vasconcelos, Hilda R. Diamond, Daniel G. Tabak, Marcello A. Barcinski, Adriana Bonomo, Elaine Sloand, Sonnie Kim, Jaroslaw Maciejewski, and Neal Young
Blood 2001 97: 333-335.
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