Administration of granulocyte colony-stimulating factor induces hyporesponsiveness to lipopolysaccharide and impairs antigen-presenting function of peripheral blood monocytes.
OBJECTIVE
The incidence and severity of acute graft-vs-host disease after allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) are not greater than those after conventional bone marrow transplantation despite infusion of more than one log greater number of donor T cells in PBSC. It has been postulated that monocytes from G-CSF-mobilized donors suppress alloreactivity of donor T cells.


METHODS
We investigated the phenotype and function of monocytes in normal individuals receiving 10 microg/kg of G-CSF for 4 days.


RESULTS
Monocytes were phenotypically and functionally different after G-CSF administration from steady-state monocytes. They were characterized by an increased CD14(+)CD16(+) subpopulation, reduced expression of HLA-DR, and diminished ability to produce tumor necrosis factor-alpha and interleukin-10 to lipopolysaccharide, compared with steady-state monocytes. These alterations were not replicated by culturing monocytes with G-CSF in vitro, suggesting an indirect effect of G-CSF. In addition, the antigen-presenting function of G-CSF-mobilized monocytes was impaired.


CONCLUSIONS
Hyporesponsiveness of G-CSF-treated monocytes to lipopolysaccharide with regard to tumor necrosis factor-alpha production, together with impaired antigen-presenting function, may be responsible for the unexpectedly low incidence of graft-vs-host disease after G-CSF-mobilized PBSC transplantation.
Sunami
K
K
Department of Biopathological Science, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools, Okayama, Japan. kazusuna@pop12.odn.ne.jp
Teshima
T
T
Nawa
Y
Y
Hiramatsu
Y
Y
Maeda
Y
Y
Takenaka
K
K
Shinagawa
K
K
Ishimaru
F
F
Ikeda
K
K
Niiya
K
K
Harada
M
M
D017951:Antigen Presentation / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000493:pharmacokinetics*
D016207:Cytokines; D008070:Lipopolysaccharides; D016179:Granulocyte Colony-Stimulating Factor