Role of macrophages in the candidacidal activity of liposomal amphotericin B.

The role of macrophage activation in the candidacidal activity of liposome-incorporated (L) amphotericin B was investigated. Macrophages treated with L-amphotericin B killed Candida albicans more effectively than did macrophages treated with free (F) amphotericin B. However, macrophages treated with neither F- nor L-amphotericin B killed amphotericin B-resistant Candida tropicalis. In vivo stimulation of macrophages by intraperitoneal administration of thioglycollate, Freund's complete adjuvant, or heat-killed C. albicans followed by in vitro treatment with F- or L-amphotericin B, did not enhance their candidacidal activity. Intravenous administration of F- or L-amphotericin B did not augment the candidacidal activity of macrophages sensitized in vivo; however, sensitized macrophages showed enhanced killing compared with resident unstimulated cells. These studies suggest that macrophage-mediated enhancement of C. albicans killing may be due to uptake, transport, and delivery of L-amphotericin B to infected sites rather than to macrophage activation.