In vivo metabolic response of hepatic nonparenchymal cells and leukocytes to granulocyte-macrophage colony-stimulating factor.

Abstract

This study investigates the in vivo glucose utilization of various immune-competent cells after an intra-arterial injection of a nonlethal dose (30 micrograms/kg body weight) of murine recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Injection of GM-CSF resulted in a rapid but transient reduction in the number of circulating neutrophils. After 20 min the number of neutrophils returned to normal values, and by 4 h it was about 80% greater than in time-matched saline-injected controls. One hour after the treatment, neutrophils were accumulated in the livers of GM-CSF-injected animals but not in control livers. In vivo glucose utilization by circulating neutrophils and mononuclear cells and various liver cell types was investigated by combining the 2-deoxyglucose tracer technique with cell isolation procedures. GM-CSF increased the in vivo glucose utilization of circulating and infiltrating neutrophils by more than 200%. Glucose utilization by circulating mononuclear cells was also doubled. After GM-CSF injection, glucose utilization by Kupffer cells was increased by 130% and by hepatic endothelial cells was increased by 60%. Indomethacin pretreatment blunted the hyperglycemia caused by GM-CSF injection; however, it did not inhibit the increased glucose utilization by immune-competent cells. This suggests that the effect of GM-CSF on glucose utilization by these cells is not mediated by prostanoids and is at least partially independent of the mass action of elevated glucose concentration. These findings indicate that GM-CSF may be an important member of the cytokine cascade that mediates the acute in vivo metabolic response of immune-competent cells in sepsis or endotoxemia.