In vivo induction of functional Fc gammaRI (CD64) on neutrophils and modulation of blood cytokine mRNA levels in cancer patients treated with G-CSF (rMetHuG-CSF)

Br J Haematol. 1998 Mar;100(3):550-6. doi: 10.1046/j.1365-2141.1998.00597.x.

Abstract

Neutrophils from 13 children who received G-CSF for the collection of peripheral blood progenitors while they were in haematological steady state were studied at various times after G-CSF injection for Fc gammaR expression (Fc gammaRI or CD64, Fc gammaRII or CD32, and Fc gammaRIII or CD16) and for their ability to exert antibody-dependent cell cytotoxicity (ADCC) through Fc gammaRI. Changes in IFNgamma, IL8, IL10, MCP1 and TNF alpha mRNA levels in peripheral blood cells were also studied 4 h and 24 h after the first G-CSF injection. Fc gammaRI expression increased strongly after 24 h and then remained at the same level throughout treatment. In contrast, Fc gammaRIII expression sharply decreased at day 1 and diminished even further thereafter. No change in Fc gammaRII was observed. ADCC exerted by neutrophils through Fc gammaRI started to increase after 24 h with the peak level at day 5. Cytokine mRNA analyses indicated a reproducible and strong increase of IL8 mRNA (11/13 children) after 24 h, whereas the changes in the mRNA levels of the other cytokines tested were more heterogenous (TFNgamma: three; IL10: six; MCP1: five: TNF alpha: four, of the 13 children). Therefore this study opens the way to an optimized therapeutic schedule for the combined use of G-CSF and monoclonal antibodies in adjuvant immuno-intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • Child
  • Child, Preschool
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Hematopoietic Stem Cell Mobilization
  • Humans
  • Infant
  • Interleukin-8 / pharmacology
  • Leukocyte Count
  • Male
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neutrophils / immunology*
  • RNA, Messenger / metabolism
  • Receptors, IgG / immunology*
  • Recombinant Proteins
  • Up-Regulation

Substances

  • Cytokines
  • Interleukin-8
  • RNA, Messenger
  • Receptors, IgG
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Filgrastim