Recombinant Murine Granulocyte-Macrophage Colony-Stimulating Factor Augments Neutrophil Recovery and Enhances Resistance to Infections in Myelosuppressed Mice

Abstract

The ability of recombinant murine granulocyte-macrophage colony-stimulating factor(rmGM-CSF) to protect myelosuppressed mice against lethal infections was evaluated. In mice myelosuppressed by cyclophosphamide, subcutaneously administeredrm GM-CSF was a potent stimulus of granulopoiesis by increasing the number of GM-CSP-responsive precursorcellsin bonemarrow followed by a profound neutrophilia. Neutrophil recovery was augmented by rmGM-CSF in a dose-dependent manner at daily doses of 0.6–5.0 µg/mouse. In addition, rmGM-CSF increased the functional activity of circulating neutrophils at similar doses. When rmGM-CSF was administered to neutropenic mice before experimentally induced Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections, it protected against these lethal infections, resulting in increased numbers of survivors. These data suggest that rmGM-CSF protects neutropenic mice from lethal infections, probably by augmenting neutrophil recovery after myelosuppression and activation of mature cells.