title: Acute G-CSF therapy is not protective during lethal E. coli sepsis.
abstract: We investigated whether decreases in circulating polymorphonuclear neutrophils (PMN) during lethal Escherichia coli (E. coli) sepsis in canines are related to insufficient host granulocyte colony-stimulating factor (G-CSF). Two-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -noninfected fibrin clots surgically placed. By 10 to 12 h following clot, both infected survivors and nonsurvivors had marked increases (P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ml +/- SE, 1,931 +/- 364 and 2,779 +/- 681, respectively) compared with noninfected controls (134 +/- 79), which decreased at 24 to 48 h. Despite increases in G-CSF, infected clot placement caused delayed (P = 0.06) increases in PMN (mean +/- SE change from baseline in cells x 10(3)/mm(3) at 24 and 48 h) in survivors (+3.9 +/- 3.9 and +13.8 +/- 3.6) compared with noninfected controls (+13.1 +/- 2.8 and +9.1 +/- 2.5). Furthermore, infected nonsurvivors had decreases in PMN (-1.4 +/- 1.0 and -1.1 +/- 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placement and continued for 96 h to produce more rapid and prolonged high levels of G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following clot in noninfected controls, it caused much smaller increases in infected survivors and decreases in infected nonsurvivors (P = 0.03 for the ordered effect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sepsis. Other factors associated with sepsis either alone or in combination with G-CSF itself may reduce increases or cause decreases in circulating PMN.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Quezado
authors.forename: C
authors.initials: C
authors.lastname: Parent
authors.forename: W
authors.initials: W
authors.lastname: Karzai
authors.forename: M
authors.initials: M
authors.lastname: Depietro
authors.forename: C
authors.initials: C
authors.lastname: Natanson
authors.forename: W
authors.initials: W
authors.lastname: Hammond
authors.forename: R L
authors.initials: RL
authors.lastname: Danner
authors.forename: X
authors.initials: X
authors.lastname: Cui
authors.forename: Y
authors.initials: Y
authors.lastname: Fitz
authors.forename: S M
authors.initials: SM
authors.lastname: Banks
authors.forename: E
authors.initials: E
authors.lastname: Gerstenberger
authors.forename: P Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D006334:Heart Function Tests / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D017211:Treatment Failure
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor