title: Granulocyte colony-stimulating factor (G-CSF) increases histone-complexed DNA plasma levels in healthy volunteers.
abstract: Granulocyte colony-stimulating factor (G-CSF) is an activator of neutrophil granulocytes. Neutrophil extracellular traps are a defensive mechanism consisting of neutrophils, platelets, DNA, histones and antimicrobial proteins. This study was performed to determine whether G-CSF increases histone-complexed DNA in the plasma of healthy volunteers. In total, 51 healthy volunteers (25 males and 26 females) were treated with G-CSF (18 with 300 µg single dose i.v., 27 with 5 µg/kg s.c. for 4 days) and six participants received a placebo. Histone-complexed DNA was measured by enzyme immunoassay in plasma samples at predefined time points (0, 2, 4, 6, 24 h after single dose, day 1, day 2 and day 5 after repeated doses). Histone levels were quantified by Western blotting. A single dose of G-CSF rapidly increased hc-DNA by about 50 % (p < 0.05 for 2-24 h). After repeated doses the increase was even more pronounced: hc-DNA increased by about 50 % (3.0 ± 0.9, p < 0.001 after 24 h and about fourfold after 96 h (p < 0.001)). A statistical significant increase in histone levels was detected as early as 4 h after G-CSF injection (0.43 ± 0.2 vs. 1.08 ± 0.3 µg/ml; p = 0.034). In the placebo group no significant changes occurred. Moreover, significantly higher levels of hc-DNA were measured in male compared to female subjects (226 ± 43 vs. 84 ± 19, p < 0.001). G-CSF injection substantially increases hc-DNA levels in healthy volunteers. There is a significant gender difference in hc-DNA at the baseline.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Schoergenhofer
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwameis
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wohlfarth
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Brostjan
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Simon T
authors.initials: ST
authors.lastname: Abrams
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Cheng-Hock
authors.initials: CH
authors.lastname: Toh
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. bernd.jilma@meduniwien.ac.at.
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D004247:DNA / Q000097:blood*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006657:Histones / Q000097:blood*; D006801:Humans; D007124:Immunoenzyme Techniques; D007155:Immunologic Factors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry*; D055815:Young Adult
chemical_list: D006657:Histones; D007155:Immunologic Factors; D010919:Placebos; D016179:Granulocyte Colony-Stimulating Factor; D004247:DNA
keywords: G-CSF; Gender; Histones; NETs; Neutrophils