The ability of recombinant murine granulocyte-macrophage colony-stimulating factor to protect neonatal rats from septic death due to Staphylococcus aureus.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) potentiates in vitro and in vivo production of granulocytes. Also, recombinant human GM-CSF in vitro enhances functional capabilities of human granulocytes. Recombinant murine (rm) GM-CSF was administered to neonatal rats in vivo to test its ability to protect from septic death due to Staphylococcus aureus. When rmGM-CSF was given intraperitoneally 6 h before a 90% lethal dose challenge of S. aureus, peak survival was observed at a dose of 30 pg/g (54% vs. 10% in animals administered saline; P less than .001). Blood cultures were positive for S. aureus in 26 of 32 saline-treated and in 5 of 31 rmGM-CSF-treated animals (P less than .001). Numbers of blood granulocytes were significantly increased 9 h after administration of rmGM-CSF (30 pg/g) but returned to control levels by 12 h. Neither neutrophil storage nor proliferative pools were affected. Thus, rmGM-CSF significantly improved survival when given prophylactically in a neonatal rat model of infection.
Department of Pediatrics, University of Texas Medical School, Houston 77030.
R W
RW
Frenck
G
G
Sarman
T E
TE
Harper
E S
ES
Buescher
D000818:Animals; D000831:Animals, Newborn; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000276:immunology*; D006133:Growth Substances / Q000627:therapeutic use*; D007958:Leukocyte Count; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000517:prevention & control*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor