Recombinant murine granulocyte-macrophage colony-stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice.
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 administered rmGM-CSF was a potent stimulus of granulopoiesis by increasing the number of GM-CSF-responsive precursor cells in bone marrow 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 micrograms/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.
Mayer
P
P
Sandoz Research Center, Vienna, Austria.
Schütze
E
E
Lam
C
C
Kricek
F
F
Liehl
E
E
D000818:Animals; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000276:immunology*; D002177:Candidiasis / Q000517:prevention & control; D003520:Cyclophosphamide; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D051379:Mice; D009503:Neutropenia / Q000139:chemically induced / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects*; D009894:Opportunistic Infections / Q000276:immunology / Q000517:prevention & control*; D011552:Pseudomonas Infections / Q000517:prevention & control; D011994:Recombinant Proteins / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000517:prevention & control
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide