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.

Autor: Weiss, Manfred, Voglic, Sami, Harms-Schirra, Britt, Lorenz, Ingrid, Lasch, Britta, Dumon, Kristoffel, Gross-Weege, Wilhelm, Schneider, Elisabeth Marion
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Zdroj: Intensive Care Medicine; Jun2003, Vol. 29 Issue 6, p904-914, 11p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
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