Protection against gram-negative bacteremia in neutropenic mice with recombinant granulocyte-macrophage colony-stimulating factor.

TitleProtection against gram-negative bacteremia in neutropenic mice with recombinant granulocyte-macrophage colony-stimulating factor.
Publication TypeJournal Article
Year of Publication1990
AuthorsBermudez LE, Martinelli JC, Gascon R, Wu M, Young LS
JournalCytokine
Volume2
Issue4
Pagination287-93
Date Published1990 Jul
ISSN1043-4666
KeywordsAnimals, Blood Bactericidal Activity, Cyclophosphamide, Female, Granulocyte-Macrophage Colony-Stimulating Factor, Immunoglobulin G, Leukocyte Count, Macrophage Activation, Mice, Mice, Inbred Strains, Neutropenia, Neutrophils, Peritoneal Cavity, Phagocytosis, Pseudomonas aeruginosa, Recombinant Proteins, Sepsis, Spleen, Superoxides
Abstract

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)

Alternate JournalCytokine