Effect of granulocyte colony-stimulating-factor on acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in a mu-rine model / 中国病理生理杂志

ABSTRACT

AIM:To explore the impact of granulocyte colony-stimulating factor (G-CSF) on acute graft-ver-sus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a murine model and its possible mechanisms.METHODS:Male C57BL/6 (H-2b) and BALB/c (H-2d) mice were used as the allogeneic and syngeneic donor mice , respectively .Moreover , female BALB/c mice were used as recipient mice .The recipient mice were conditioned by a single dose ( 8 Gy ) of total body irradiation ( TBI ) .The recipient mice were randomly divided into 7 groupsTBI group, Syn-BMST control group, post-Syn-BMST G-CSF administration (Syn-BMST+G-CSF) group, allo-BMT control group, post-allo-BMT G-CSF administration (allo-BMT+G-CSF)group, allo-BMST control group and post-al-lo-BMST G-CSF administration (allo-BMST+G-CSF) group.The mice in control groups and G-CSF administration groups were subcutaneous injected with 0.1 mL normal saline (NS) and 0.1 mL NS containing 2μg G-CSF per day from 1st day, respectively.The effect of G-CSF on aGVHD was evaluated by clinical manifestations and pathological changes , as well as survival time of the mice in different groups .The serum levels of IL-2, IL-4, IFN-γand TNF-αin allo-BMST and allo-BMST+G-CSF groups were detected by ELISA at 10th day.Flow cytometry was used to analyze the immunophenotypes of splenocytes at 10th day.RESULTS:The mice in TBI group were all died for hematologic failure on 9~15 d after TBI.No effect of G-CSF on the survival of the mice underwent Syn-BMST and transplantation of single allogeneic marrow cells was observed.The mean survival days in allo-BMST group and allo-BMST+G-CSF group were (34.8 ±4.5) d and (19.8 ± 6.1) d’respectively (P<0.01).Moreover, post-transplant administration of G-CSF increased the spleen total nucleated cells count (SpTNC), NK cells subset, and DC1/DC2 ratio in the spleen with over 99%of donor chimerism rate at 10th day.No difference in the levels of serum IL-2, IL-4, IFN-γand TNF-αbetween the 2 group at 10th day was found.CON-CLUSIONThe administration of G-CSF after allo-BMST significantly aggravates mouse aGVHD .The expansion of NK cells stimulated by G-CSF may be involved in the mechanism of generating alloreactivity against host cells .These results imply there may be potential risk of evoking or aggravating acute GVHD if G-CSF is administered in the early stage of clini-cal allo-HSCT.