Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis.
Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.
Weiss
M
M
Department of Anaesthesiology, Heinrich-Heine-Universitat, Dusseldorf, Germany.
Gross-Weege
W
W
Harms
B
B
Schneider
E M
EM
D000954:Antigens, Surface / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016207:Cytokines / Q000097:blood*; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D019041:L-Selectin / Q000096:biosynthesis; D007958:Leukocyte Count; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D017452:Receptors, IgG / Q000096:biosynthesis / Q000097:blood; D011994:Recombinant Proteins; D018570:Risk Assessment; D012307:Risk Factors; D018805:Sepsis / Q000453:epidemiology / Q000517:prevention & control*; D013997:Time Factors; D015854:Up-Regulation; D014947:Wounds and Injuries
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016207:Cytokines; D017452:Receptors, IgG; D011994:Recombinant Proteins; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim