title: Effect of delayed treatment with recombinant human granulocyte colony-stimulating factor on survival and plasma cytokine levels in a non-neutropenic porcine model of Pseudomonas aeruginosa sepsis.
abstract: BACKGROUND
  Neutrophils are of great importance for the host's defense against invading organisms. Granulocyte colony-stimulating factor (G-CSF) has been used to augment both the neutrophil number and function, and its prophylactic administration has proved beneficial in animal models of sepsis. However, pretreatment with G-CSF is not practical under clinical conditions. We therefore investigated the effect of recombinant human (rh)G-CSF, administered only after infection, on the survival rate as well as the hemodynamic and cytokine response of the animals.
  
  
  METHODS
  Chronically catheterized conscious pigs were challenged with Pseudomonas aeruginosa (8 x 10(7) colony-forming units kg(-1) x h(-1) for 120 h (control group, n = 10). Animals in the G-CSF group (n = 7) also received rhG-CSF (5 microg kg(-1) x day(-1)), the first dose being given 3 h after beginning bacterial infusion.
  
  
  RESULTS
  The mortality rate was 50% (5/10) and 29% (2/7) in the control and G-CSF groups, respectively (p = NS, control vs. G-CSF group). Fever, severe pulmonary hypertension, and a hyperdynamic response were recorded in all of the animals. In spite of a prompt and significant recovery from the initial leukopenia (p < .05 vs. control group), the animals of the G-CSF group showed no significant differences in the parameters investigated from those of the controls. Compared with the survivors, the interleukin-1 receptor antagonist was markedly elevated in all nonsurvivors after 6 h of sepsis (p < .05).
  
  
  CONCLUSIONS
  These data suggest that treatment with rhG-CSF after the onset of bacterial sepsis might not significantly improve the chances of survival for non-neutropenic patients.
authors.affiliation: Chirurgische Universitätsklinik, Chirurgische Forschung, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Haberstroh
authors.forename: K
authors.initials: K
authors.lastname: Wiese
authors.forename: A
authors.initials: A
authors.lastname: Geist
authors.forename: G B
authors.initials: GB
authors.lastname: Dursunoglu
authors.forename: C
authors.initials: C
authors.lastname: Gippner-Steppert
authors.forename: M
authors.initials: M
authors.lastname: Jochum
authors.forename: B U
authors.initials: BU
authors.lastname: von Specht
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality*; D001769:Blood / Q000382:microbiology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D011552:Pseudomonas Infections / Q000188:drug therapy*; D012123:Pulmonary Ventilation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000097:blood; D015996:Survival Rate; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects
chemical_list: D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor