title: G-CSF modulates cytokine profile of dendritic cells and decreases acute graft-versus-host disease through effects on the donor rather than the recipient.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. reddyvs@medicine.ufl.edu
authors.forename: V
authors.initials: V
authors.lastname: Reddy
authors.forename: G R
authors.initials: GR
authors.lastname: Hill
authors.forename: L
authors.initials: L
authors.lastname: Pan
authors.forename: A
authors.initials: A
authors.lastname: Gerbitz
authors.forename: T
authors.initials: T
authors.lastname: Teshima
authors.forename: Y
authors.initials: Y
authors.lastname: Brinson
authors.forename: J L
authors.initials: JL
authors.lastname: Ferrara
mesh_terms: 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
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor