RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ENHANCESTHE EFFECTS OF ANTIBIOTICS AGAINST MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN THE BEIGE MOUSE MODEL

Previous studies have shown that recombinant granulocyte-macrophage co lony-stimulating factor (GM-CSF) stimulates human and murine macrophag es to inhibit growth and kill intracellularly. This study shows the ef fect of GM-CSF on Mycobacterium avium complex (MAC) infection in vivo using a C57BL/6 beige mouse model of disseminated MAC infection. Furth ermore, it examined the activity of the combination of GM-CSF and amik acin or azithromycin, two antimicrobials active against MAC, on the su rvival of MAC within macrophages in vitro and in the mouse model of di sseminated infection. Although GM-CSF (25 mg/kg) induced mycobacterici dal and mycobacteriostatic activity in macrophages in vitro and in viv o, the combination of GM-CSF and amikacin (50 mg/kg) or azithromycin ( 250 mg/kg) was associated with a significant increase in killing of MA C both within cultured macrophages and in the beige mouse model. There fore, a significant reduction in the number of viable bacteria was obs erved in blood, liver, and spleen of mice treated with a combination o f GM-CSF and azithromycin or amikacin compared with control mice and t hose treated with GM-CSF or antimicrobials alone.