Effects of Therapeutic Recombinant Granulocyte Colony Stimulating Factor

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The Effects of Therapeutic Recombinant Granulocyte Colony Stimulating Factor with Intraperitoneal E. Recombinant granulocyte colony stimulating factor (G-CSF) increases circulating neutrophil number and function. Administration of G-CSF improves host defense and decreases morbidity associated with infection in immunocompromised patients and animal models. It is unclear whether therapeutic administration of G- CSF will have benefi-cial or harmful effects in immunocompetent patients at risk of or developing infection. We have shown that G-CSF pretreatment in a canine model of lethal bacterial peritonitis increases circulating neutrophil numbers, accelerates bacteria and endotoxin clearance and improves cardiovascular function and survival. In a subsequent set of studies, we evaluated the effects of G-CSF administered therapeutically at the onset of bacterial sepsis rather than prophylactically. In these studies we found that therapeutic G-CSF even if given at very high dosages did not result in increased circulating neutrophil numbers during the septic period and did not offer a protective advantage. These findings suggest that sepsis associated events may either directly inhibit the stimulatory effects of exogenous G-CSF, or alternatively result in a maximal inflammatory response by the host which is insensitive to the effects of exogenous G-CSF. These studies suggest that therapeutic administration of G-CSF in patients presenting with lethal bacterial sepsis may have little benefit.