Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibiotics against Mycobacterium avium complex infection in the beige mouse model.

TitleRecombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibiotics against Mycobacterium avium complex infection in the beige mouse model.
Publication TypeJournal Article
Year of Publication1994
AuthorsBermudez LE, Martinelli J, Petrofsky M, Kolonoski P, Young LS
JournalThe Journal of infectious diseases
Volume169
Issue3
Pagination575-80
Date Published1994 Mar
ISSN0022-1899
KeywordsAmikacin, Animals, Azithromycin, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Macrophages, Mice, Mycobacterium avium Complex, Mycobacterium avium-intracellulare Infection, Recombinant Proteins
Abstract

Previous studies have shown that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates human and murine macrophages to inhibit growth and kill intracellularly. This study shows the effect of GM-CSF on Mycobacterium avium complex (MAC) infection in vivo using a C57BL/6 beige mouse model of disseminated MAC infection. Furthermore, it examined the activity of the combination of GM-CSF and amikacin or azithromycin, two antimicrobials active against MAC, on the survival of MAC within macrophages in vitro and in the mouse model of disseminated infection. Although GM-CSF (25 mg/kg) induced mycobactericidal and mycobacteriostatic activity in macrophages in vitro and in vivo, the combination of GM-CSF and amikacin (50 mg/kg) or azithromycin (250 mg/kg) was associated with a significant increase in killing of MAC both within cultured macrophages and in the beige mouse model. Therefore, a significant reduction in the number of viable bacteria was observed in blood, liver, and spleen of mice treated with a combination of GM-CSF and azithromycin or amikacin compared with control mice and those treated with GM-CSF or antimicrobials alone.

Alternate JournalJ. Infect. Dis.