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

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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 107 colony-forming units kg-1 · h-1 for 120 h (control group, n = 10). Animals in the G-CSF group (n = 7) also received rhG-CSF (5 μg kg-1 · 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.

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