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.
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.
Haberstroh
J
J
Chirurgische Universitätsklinik, Chirurgische Forschung, Freiburg, Germany.
Wiese
K
K
Geist
A
A
Dursunoglu
G B
GB
Gippner-Steppert
C
C
Jochum
M
M
von Specht
B U
BU
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
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