Human lactoferrin-derived peptide's antifungal activities against disseminated Candida albicans infection.
BACKGROUND
Because the human lactoferrin-derived peptide, hLF(1-11), exerts potent in vitro candidacidal activity, we investigated whether it displays antifungal activity against disseminated Candida albicans infections.


METHODS
Neutropenic mice were intravenously infected with C. albicans and, 24 h later, were injected with hLF(1-11); 18 h later, the number of viable yeasts in the kidneys was determined microbiologically, the size and number of infectious foci were determined histologically, and serum cytokine levels were determined by immunoassays.


RESULTS
hLF(1-11) was effective (maximum reduction, 1.5 logs) against disseminated C. albicans infections, and its antifungal activity leveled off at a concentration of 0.4 ng of hLF(1-11)/kg of body weight. The antifungal activity of hLF(1-11) was increased in mice injected with interleukin (IL)-10 neutralizing antibodies, which suggests that IL-10 reduces the antifungal activity of hLF(1-11). In agreement with this result was the finding that injection of high doses of hLF(1-11) into infected mice was accompanied by increased levels of IL-10 in serum. Microscopic analysis revealed that infectious foci in kidneys of hLF(1-11)-treated mice contained mainly blastoconidia, whereas filamentous forms were abundant in untreated mice. The peptide inhibited the in vitro morphological transition of C. albicans, in a dose-dependent manner. : hLF(1-11) is effective against disseminated C. albicans infections; and its effects on C. albicans viability and virulence and on host cells may explain this antifungal activity.
Lupetti
Antonella
A
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Brouwer
Carlo P J M
CP
Bogaards
Sylvia J P
SJ
Welling
Mick M
MM
de Heer
Emile
E
Campa
Mario
M
van Dissel
Jaap T
JT
Friesen
Robert H E
RH
Nibbering
Peter H
PH
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D002352:Carrier Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007674:Kidney Diseases / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D007781:Lactoferrin; D051379:Mice; D009503:Neutropenia; D013047:Specific Pathogen-Free Organisms
D000935:Antifungal Agents; D002352:Carrier Proteins; C490098:LTF protein, human; D016753:Interleukin-10; D015725:Fluconazole; D007781:Lactoferrin