Macrophage colonystimulating factor induction of enhanced macrophage anticryptococcal activity: synergy with fluconazole for killing. J Infect Dis

Enhancement of anticryptococcal activity in macrophages by macrophage colony-stimulating factor (M-CSF) and possible synergy between macrophages and fluconazole for killing of Cryp-tococcus neoformans were tested. M-CSF (48 h)-treated macrophages underwent dramatic mor-phologic changes and inhibited cryptococcal multiplication by 96 % ± 4%, which wasgreater (P <.001) than that of macrophages cultured in medium alone. M-CSF (5000 units/ml.) induced optimal anticryptococcal activity but did not increase percentage of phagocytosis. NG-mono-methyl-L-arginine did not affect enhanced fungistatic activity. For a very fluconazole-sensitive isolate, fungistatic macrophages synergized with fungistatic doses of fluconazole for killing; for a less sensitive isolate, synergywas significant only when macrophages wereactivated with M-CSF or interferon-v plus lipopolysaccharide; for a fluconazole-resistant isolate, macrophages col-laborated with fluconazole for additive fungistasis but not killing, and M-CSF-treated macro-phages were significantly more fungistatic with fluconazole than were nonactivated macro-phages. Cryptococcus neoformans is an opportunistic fungal patho-gen causing serious systemic infections in a number of clini-'cal situations. Cryptococcosis in AIDS, leukemia, and cance