Using a multifactorial study design, we previously showed that site and severity of infection may fundamentally alter the effects of prophylactic granulocyte colony-stimulating factor (G-CSF) in Escherichia coli -infected rats. With intravenous E. coli challenge, G-CSF pretreatment increased lethality at all bacterial dosages. However, with intrabronchial and intraperitoneal challenge, G-CSF worsened survival at intermediate bacterial dosages (LD50) but improved survival with high bacterial dosages (LD90). We have continued studies using this multifactorial design to investigate the mechanisms underlying these disparate effects of G-CSF. These ongoing studies attempt to characterize the intravascular or extravascular host defense and inflammatory response associated with G-CSF to suggest reasons for this agent's divergent effects during differing types of bacterial challenge.
