Effects of exogenous recombinant human granulocyte colony-stimulating factor (filgrastim, rhG-CSF) on neutrophils of critically ill patients with systemic inflammatory response syndrome depend on endogenous G-CSF plasma concentrations on admission

Intensive Care Med. 2003 Jun;29(6):904-914. doi: 10.1007/s00134-003-1734-y. Epub 2003 Apr 8.

Abstract

Objective: To investigate the effects of exogenous recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) application on the neutrophils of patients at risk of sepsis following major trauma or operation.

Design: Randomized controlled trial.

Setting: Surgical intensive care unit and research laboratory of a university hospital.

Patients: Twenty-seven patients with systemic inflammatory response syndrome (SIRS).

Interventions: Thirteen patients were treated with filgrastim (1 micro g.kg.24 h) for 10 days as a continuous infusion. Fourteen patients served as controls.

Measurements and results: Surface expression of FcgammaR type I (CD64), phagocytosis of E. coli, and the E. coli-induced oxidative burst of neutrophils were tested by flow cytometry. On the first postoperative/posttraumatic day, endogenous G-CSF plasma concentrations were <300 pg/ml in seven controls (subgroup 1) and nine filgrastim patients (subgroup 3), and were already elevated with >500 pg/ml in seven controls (subgroup 2) and four filgrastim patients (subgroup 4). G-CSF values ( P=0.0026, subgroup 1/3; P=0.0167, 2/4), neutrophil counts ( P=0.0026, 1/3; P=0.0167, 2/4), and CD64 expression ( P=0.0013, 1/3) were higher in filgrastim-treated than non-treated subgroups, but not phagocytic and burst activities. From day zero to day 1, phagocytosis decreased in subgroups 1 (5/7 patients) and 3 (5/9), but increased in subgroups 2 (5/7) and 4 (3/4), and respiratory burst activity decreased in subgroup 3 (8/9).

Conclusions: Besides activation of neutrophil maturation, low-dose rhG-CSF application in postoperative patients with SIRS has different effects on neutrophil functions, in part depending on already endogenously produced G-CSF.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Female
  • Filgrastim
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / blood*
  • Granulocyte Colony-Stimulating Factor / drug effects*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Infusions, Intravenous
  • Length of Stay / statistics & numerical data
  • Leukocyte Count
  • Male
  • Middle Aged
  • Multiple Trauma / complications
  • Neutrophils / chemistry
  • Neutrophils / drug effects*
  • Phagocytosis
  • Prospective Studies
  • Receptors, IgG / analysis
  • Receptors, IgG / drug effects
  • Recombinant Proteins
  • Respiratory Burst
  • Risk Factors
  • Surgical Procedures, Operative / adverse effects
  • Systemic Inflammatory Response Syndrome / blood*
  • Systemic Inflammatory Response Syndrome / drug therapy*
  • Systemic Inflammatory Response Syndrome / etiology
  • Treatment Outcome

Substances

  • Receptors, IgG
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Filgrastim