Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibiotics against Mycobacterium avium complex infection in the beige mouse model.
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.
Bermudez
L E
LE
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115.
Martinelli
J
J
Petrofsky
M
M
Kolonoski
P
P
Young
L S
LS
D000583:Amikacin / Q000627:therapeutic use; D000818:Animals; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D015269:Mycobacterium avium Complex / Q000187:drug effects; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017963:Azithromycin; D000583:Amikacin