EFFECTS OF GRANULOCYTE COLONY-STIMULATING FACTOR IN MODIFYING MORTALITY FROM PSEUDOMONAS-AERUGINOSA PNEUMONIA AFTER HEMORRHAGE

Background and Methods: Alterations in immune function occurring after hemorrhage and trauma may contribute to the high occurrence rates of nosocomial pneumonia, multiorgan system failure, morbidity, and mortality in this setting. Therapy with granulocyte colony-stimulating factor (G-CSF) can increase neutrophil numbers and function, and enhance resistance to infection in experimental and clinical settings associated with abnormal immune function. To investigate whether treatment with G-CSF could increase resistance to pneumonia after hemorrhage, we bled mice 30% of the blood volume and treated them with various doses of G-CSF, starting either immediately or 2 days after hemorrhage. Pseudomonas aeruginosa pneumonia was induced by the intratracheal instillation of 2 x 10(7) colony-forming units of P. aeruginosa 4 days after blood loss, and mortality was assessed over the next 7 days. Results: Treatment of mice with 100 or 500-mu-g/kg/day G-CSF, but not with 50-mu-g/kg/day, resulted in significant increases in the numbers of circulating polymorphonuclear cells. Platelet counts significantly decreased in mice given 500-mu-g/kg/day G-CSF. Mice given 100-mu-g/kg/day G-CSF starting 2 days after blood loss had improved outcome compared with vehicle-treated controls (38% survival rate in the G-CSF treated group vs. 8% in controls, p < .05). There also was a trend toward an improved survival rate in mice treated with 50-mu-g/kg/day G-CSF for 4 days after hemorrhage (46% survival rate in G-CSF treated vs. 17% in controls). Conclusions: G-CSF prophylactically administered after hemorrhage can improve survival from pneumonia due to P. aeruginosa. However, the protection afforded by G-CSF was highly dependent on the dosing schedule used.