G-CSF modulates cytokine profile of dendritic cells and decreases acute graft-versus-host disease through effects on the donor rather than the recipient.
Allogeneic peripheral blood stem cell transplantation (PBSCT) is increasingly used instead of bone marrow transplantation, particularly in HLA identical sibling pairs. Despite the presence of significantly increased numbers of T cells in the PBSC graft, acute graft-versus-host disease (GVHD) is not increased. We have investigated whether granulocyte-colony stimulating factor (G-CSF) administration to PBSCT recipients, both with and without donor G-CSF pretreatment, further modulates acute GVHD in a murine model of PBSCT. Recipients of G-CSF mobilized splenocytes showed a significantly improved survival (P<0.001) and a reduction in GVHD score and serum LPS levels compared with control recipients. G-CSF treatment of donors, rather than recipients, had the most significant effect on reducing levels of tumor necrosis factor (TNFalpha) 7 days after transplantation. As a potential mechanism of the reduction in TNFalpha, we demonstrate G-CSF decreased dendritic cells TNFalpha, and interleukin-12 production to lipopolysaccharide. In conclusion, G-CSF modulates GVHD predominantly by its effects on donor cells, reducing the production of TNFalpha. G-CSF treatment of bone marrow transplantation recipients, without pretreatment of the donor, does not have an impact on acute GVHD.
Reddy
V
V
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. reddyvs@medicine.ufl.edu
Hill
G R
GR
Pan
L
L
Gerbitz
A
A
Teshima
T
T
Brinson
Y
Y
Ferrara
J L
JL
D000818:Animals; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000032:analysis*; D003713:Dendritic Cells / Q000737:chemistry*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D008070:Lipopolysaccharides / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000528:radiation effects; D015996:Survival Rate; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014916:Whole-Body Irradiation
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor