Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani: comparison with Aspergillus fumigatus.
OBJECTIVE
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. fumigatus 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 H2O2 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.
Dotis
John
J
Laboratory of Infectious Diseases, 3rd Department of Paediatrics, School of Medicine, Aristotle University, Hippokration Hospital, Thessaloniki 54642, Greece.
Simitsopoulou
Maria
M
Dalakiouridou
Maria
M
Konstantinou
Thomai
T
Panteliadis
Christos
C
Walsh
Thomas J
TJ
Roilides
Emmanuel
E
D000328:Adult; D000666:Amphotericin B / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000276:immunology; D004338:Drug Combinations; D005670:Fusarium / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D025301:Hyphae / Q000276:immunology / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D013778:Tetrazolium Salts / Q000378:metabolism
D004338:Drug Combinations; D007155:Immunologic Factors; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C068538:liposomal amphotericin B; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D000666:Amphotericin B