Granulocyte colony-stimulating factor produces a decrease in IFNgamma and increase in IL-4 when administrated to healthy donors.

ABSTRACT

Hematopoietic stem cells transplantation (HSCT) is the leading curative therapy for a variety of hematological and hereditary diseases; however, graft versus host disease (GVHD), an immunologic phenomenon that is favored by Th1 cytokines and cytotoxic cells from donors, is present frequently and is one of the most important causes of transplant related mortality. Peripheral blood HSCT is the preferred source of stem cells in almost 100% of the cases of autologous HSCT and in 70% of allogeneic transplants. The best mobilizing agent to get the stem cells out from the bone marrow is the Granulocyte-Colony Stimulating Factor (G-CSF). In this work, our main objective was to study a possible correlation between the graft cell dose and the patient's clinical outcome. We evaluated the immunologic changes produced by G-CSF in the lymphocyte and cytokine profiles in allogeneic HSC donors. HSC from twelve donors were mobilized with G-CSF at 16 microg/kg/day, for 5 days. Basal Peripheral Blood (BPB), Mobilized Peripheral Blood (MPB), and aphaeresis mononuclear cells (G-MNC) samples were taken from all donors. Using flow cytometry, we quantified CD19(+), CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), NK, NKT, DC1, and DC2 cells. Cytokines were determined by ELISA in culture supernatants. CD19(+) (p = 0.001), DC1 (p < 0.002) and DC2 (p < 0.001) cells were increased in MPB with respect to BPB. An increase in Th2 cytokines such as (IL-4) and a decrease in Th1 cytokines (IFNgamma, IL-2) were also found in MPB samples. In conclusion, Th1 and Th2 cytokines are relevant in predicting the clinical outcome after allogeneic peripheral blood HSCT.