Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo

Peripheral blood stem cell (PBSC) transplantation is successful in improvin g engraftment without increasing acute graft-versus-host disease (GVHD), de spite much larger numbers of T cells in unmanipulated PBSCs than in bone ma rrow grafts. In mouse models and retrospective human studies, granulocyte c olony-stimulating factor (G-CSF) therapy has been associated with less acut e GVHD. We studied the effect of G-CSF on interferon (IFN)-gamma and IL-4 e xpression in CD4(+) lymphocytes. CD4(+) cells co-cultivated with G-CSF and stimulated with PHA or CD3 monoclonal antibodies showed significant decreas es in IFN-gamma and increases in IL-4 expression (n = 13; P <.01), G-CSF ap peared to have a direct effect on CD4(+) cells independent of monocytes pre sent in the culture because purified CD4(+) bells exposed to G-CSF, washed, and cocultivated with untreated monocytes demonstrated similar changes in IFN-gamma and IL-4 expression, whereas untreated CD4(+) cells cocultured wi th G-CSF-stimulated monocytes behaved as controls. We then studied peripher al blood mononuclear cells (PBMCs) from G-CSF-mobilized PBSC donors. When t heir PBMCs were cultured with PHA or CD3 monoclonal antibody, the percent o f IFN-gamma-expressing cells decreased by a mean of 55% and 42%, respective ly, 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-gamma-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. Thes e results suggest that G-CSF decreases IFN-gamma and increases IL-4 product ion in vitro and in vivo and likely modulates a balance between TH1 and TH2 cells, an effect that may be important in PBSC transplantation. (Blood. 20 00;95:2269-2274) (C) 2000 by The American Society of Hematology.