title: Human lactoferrin-derived peptide's antifungal activities against disseminated Candida albicans infection.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Antonella
authors.initials: A
authors.lastname: Lupetti
authors.forename: Carlo P J M
authors.initials: CP
authors.lastname: Brouwer
authors.forename: Sylvia J P
authors.initials: SJ
authors.lastname: Bogaards
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
authors.forename: Mario
authors.initials: M
authors.lastname: Campa
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: Robert H E
authors.initials: RH
authors.lastname: Friesen
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nibbering
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D002352:Carrier Proteins; C490098:LTF protein, human; D016753:Interleukin-10; D015725:Fluconazole; D007781:Lactoferrin