title: Administration of granulocyte colony-stimulating factor induces hyporesponsiveness to lipopolysaccharide and impairs antigen-presenting function of peripheral blood monocytes.
abstract: 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.
authors.affiliation: Department of Biopathological Science, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools, Okayama, Japan. kazusuna@pop12.odn.ne.jp
authors.forename: K
authors.initials: K
authors.lastname: Sunami
authors.forename: T
authors.initials: T
authors.lastname: Teshima
authors.forename: Y
authors.initials: Y
authors.lastname: Nawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hiramatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Takenaka
authors.forename: K
authors.initials: K
authors.lastname: Shinagawa
authors.forename: F
authors.initials: F
authors.lastname: Ishimaru
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Niiya
authors.forename: M
authors.initials: M
authors.lastname: Harada
mesh_terms: 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*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016179:Granulocyte Colony-Stimulating Factor