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.
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.


METHODS
Randomized controlled trial.


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


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


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


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.
Weiss
Manfred
M
Anaesthesiology, Universitaetsklinikum Ulm, Steinhoevelstrasse 9, 89075, Ulm, Germany. manfred.weiss@medizin.uni-ulm.de.
Voglic
Sami
S
Anaesthesiology, Universitaetsklinikum Ulm, Steinhoevelstrasse 9, 89075, Ulm, Germany.
Harms-Schirra
Britt
B
Experimental Anaesthesiology, Universitaetsklinikum Ulm, Ulm, Germany.|EVOTEC Technologies, Max-Planck-Strasse 15a, 40699, Erkrath, Germany.
Lorenz
Ingrid
I
Experimental Anaesthesiology, Universitaetsklinikum Ulm, Ulm, Germany.
Lasch
Britta
B
Experimental Anaesthesiology, Universitaetsklinikum Ulm, Ulm, Germany.
Dumon
Kristoffel
K
Surgery, Heinrich-Heine-Universitaet Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany.
Gross-Weege
Wilhelm
W
Surgery, Heinrich-Heine-Universitaet Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany.
Schneider
Elisabeth Marion
EM
Experimental Anaesthesiology, Universitaetsklinikum Ulm, Ulm, Germany.
D000328:Adult; D000368:Aged; D005260:Female; D000069585:Filgrastim; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood* / Q000187:drug effects* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007902:Length of Stay / Q000706:statistics & numerical data; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000150:complications; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects*; D010587:Phagocytosis; D011446:Prospective Studies; D017452:Receptors, IgG / Q000032:analysis / Q000187:drug effects; D011994:Recombinant Proteins; D016897:Respiratory Burst; D012307:Risk Factors; D013514:Surgical Procedures, Operative / Q000009:adverse effects; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
D017452:Receptors, IgG; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim