Granulocyte-macrophage colony-stimulating factor enhances neutrophil function in acquired immunodeficiency syndrome patients.
We conducted a clinical trial of human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in leukopenic patients with acquired immunodeficiency syndrome (AIDS) and analyzed neutrophil function before, during, and after in vivo administration of rGM-CSF. Prior to GM-CSF infusion, AIDS patients' neutrophil superoxide generation and neutrophil antibody-dependent cell-mediated cytotoxicity were enhanced normally by in vitro exposure to GM-CSF. Neutrophil phagocytosis and intracellular killing of Staphylococcus aureus were also normal in the majority of these patients. Two patients, however, had discrete neutrophil functional defects: one in phagocytosis and one in intracellular killing. During the period of GM-CSF infusion, these abnormalities were corrected. The number of circulating neutrophils increased in all patients treated with GM-CSF in a dose-dependent manner. Neutrophils produced in vivo in response to GM-CSF administration functioned normally and there was evidence for neutrophil priming and activation in vivo. We conclude that GM-CSF treatment of AIDS patients leads to the production of functionally active neutrophils, suggesting therapeutic potential for GM-CSF in the treatment of patients with impaired host defense.
Baldwin
G C
GC
Division of Hematology-Oncology, University of California School of Medicine, Los Angeles 90024-1678.
Gasson
J C
JC
Quan
S G
SG
Fleischmann
J
J
Weisbart
R
R
Oette
D
D
Mitsuyasu
R T
RT
Golde
D W
DW
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001769:Blood; D001770:Blood Bactericidal Activity / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007167:Immunotherapy; D066298:In Vitro Techniques; D009504:Neutrophils / Q000276:immunology*; D010101:Oxygen Consumption; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor