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 keen used to augment both the neutrophil number and function, and its prophylactic administration has proved beneficial in animal m odels of sepsis. However, pretreatment with G-CSF is not practical und er clinical conditions. We therefore investigated the effect of recomb inant human (rh)G-CSF, administered only after infection, on the survi val rate as well as the hemodynamic and cytokine response of the anima ls. Methods: Chronically catheterized conscious pigs were challenged w ith Pseudomonas aeruginosa (8 X 10(7) 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 mu g kg(-1) . day(-1)), the first dose be ing given 3 h after beginning bacterial infusion. Results: The mortali ty 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 pulmonar y hypertension, and a hyperdynamic response were recorded in all of th e animals. In spite of a prompt and significant recovery from the init ial leukopenia (p < .05 vs. control group), the animals of the G-CSF g roup showed no significant differences in the parameters investigated from those of the controls. Compared with the survivors, the interleuk in-1 receptor antagonist was markedly elevated in all nonsurvivors aft er 6 h of sepsis (p < .05). Conclusions: These data suggest that treat ment with rhG-CSF after the onset of bacterial sepsis might not signif icantly improve the chances of survival for non-neutropenic patients.