Therapeutic Use of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Neonatal Rats with Type III Group B Streptococcal Sepsis

Abstract

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as therapy in neonatal sepsis has been proposed because of observed defects in polymorphonuclear leukocyte (PMNL) production and function in infected neonates. Newborn rats were infected intraperitoneally (ip) with type III group B streptococcus (III-GBS) and effects of treatment with rhGM-CSF given ip 7-19 h after infection were studied. Overall mortality was 67% in controls and 37% in animals treated with rhGM-CSF (P = .003). No changes in peripheral blood PMNL number or oxidative metabolic function were found in infected or uninfected animals given rhGM-CSF compared with controls. In uninfected animals, there was an increase in the oxidative burst of peritoneal cells at 3.5 h (P = .043) and in the numbers of peritoneal cells at 3 h (P = .001) in animals receiving ip rhGM-CSF compared with controls. Phagocyte priming, cellular influx into the peritoneum, or both appear to contribute to the decreased mortality observed in this model of rhGM-CSF therapy of III-GBS disease in neonates.