Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani: Comparison with Aspergillus fumigatus

Abstract

Objectives: Lipid formulations of amphotericin B (AMBF) are widely used in the treatment of life-threatening infections caused by Aspergillus fumigatus and Fusarium solani. We aimed to compare the immunomodulatory effects of four AMBF, deoxycholate (DAMB), liposomal (LAMB), lipid complex (ABLC) and colloidal dispersion (ABCD), on the oxidative antifungal activities of human neutrophils (PMNs) and monocytes (MNCs) against hyphae of A. fumigatus and F. solani. Methods: Human PMNs and MNCs were pre-incubated with 1 or 5 mg/L DAMB and 5 or 25 mg/L for each of LAMB, ABLC and ABCD. Hyphal damage was then assessed by XTT assay, and O2- production was assessed by cytochrome c assay. Results: All agents resulted in increased hyphal damage induced by phagocytes against both A. fumigatu s and F. solani (P < 0.05). The high concentrations of AMBF elicited higher phagocyte-induced hyphal damage of both fungi than the low concentrations. There was, however, no consistent superiority of any of the AMBF or substantial effector cell:target ratio-dependent differences in the degree of hyphal damage enhancement. By comparison, O2- produced by PMNs or MNCs upon hyphal challenge was not generally affected by any of the AMBF. F. solani hyphae were significantly more resistant to H2 O2 than A. fumigatus. Conclusions: These findings suggest that AMBF have enhancing effects of variable degree on phagocyte-induced hyphal damage of A. fumigatus and F. solani. Other fungicidal mechanisms, perhaps non-oxidative, are more likely to mediate these immunomodulatory effects of AMBF on host defence against the two medically important filamentous fungi. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.