Protection against gram-negative bacteremia in neutropenic mice with recombinant granulocyte-macrophage colony-stimulating factor.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates production of neutrophils in bone marrow and may decrease the incidence of infection during neutropenia. We evaluated the protective role of recombinant GM-CSF against Pseudomonas aeruginosa challenge in neutropenic mice. CD-1 mice treated with cyclophosphamide on days 1 and 2 of the experiment were given GM-CSF (1, 2, or 4 micrograms/day) starting at day 4 of the experiment according to the following protocol: 1) 1 microgram of GM-CSF 2 hr and 24 hr after challenge; 2) 1 microgram 24 hr before challenge, 2 hr and 24 hr after challenge; 3) 2 micrograms injected 24 hr before and 2 hr after challenge; 4) 2 micrograms given 24 hr before and 2 micrograms given 2 hr and 24 hr after challenge; 5) 4 micrograms administered 2 hr and 24 hr after challenge; and 6) saline and bovine albumin controls. The number of blood neutrophils by days 4 and 5 was similar for GM-CSF-treated and untreated animals. Survival was significantly greater in animals given 2 micrograms of GM-CSF at 24 hr before and at 2 hr and 24 hr after challenge with Pseudomonas. Neutrophils and splenic macrophages obtained from GM-CSF-treated mice (2 micrograms/animal) produced significantly greater amounts of O2- (204 +/- 36 nmoles/10(5) cells) than controls (21 +/- 10 nmoles/10(5) cells). Additionally, neutrophils and macrophages from GM-CSF-treated mice killed significantly more bacteria (P. aeruginosa) in vitro and had a greater number of C3b and Fc receptors (78 +/- 12% and 89 +/- 8%) than did cells obtained from control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Bermudez
L E
LE
Kuzell Institute for Arthritis and Infectious Diseases, Medical Research Institute of San Francisco, CA 94115.
Martinelli
J C
JC
Gascon
R
R
Wu
M
M
Young
L S
LS
D000818:Animals; D001770:Blood Bactericidal Activity; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009503:Neutropenia / Q000188:drug therapy*; D009504:Neutrophils / Q000502:physiology; D010529:Peritoneal Cavity / Q000166:cytology; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013481:Superoxides / Q000378:metabolism
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide