title: Protective effects of human lactoferrin during Aggregatibacter actinomycetemcomitans-induced bacteremia in lactoferrin-deficient mice.
abstract: Aggregatibacter actinomycetemcomitans, a periodontopathogen, has been associated with several systemic diseases. Herein, we report the protective effect of human lactoferrin (hLF) during A. actinomycetemcomitans bacteremia in lactoferrin knockout (LFKO(-/-)) mice. The prophylactic, concurrent, and therapeutic intravenous (i.v.) administrations of hLF significantly cleared the bacteria from blood and organs. Nevertheless, all modes of hLF administration significantly decreased the concentrations of serum proinflammatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, and IL-12p70. Additionally, hLF administration significantly decreased hepatic and splenic proinflammatory cytokine expression levels compared to those in the non-hLF-treated group. Furthermore, administration of hLF decreased the serum C-reactive protein level, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) gene expression levels in liver and spleen. hLF treatment has also resulted in a 6-fold decrease in spleen weight with the migration of typical inflammatory cells in infected mice as a result of decreased inflammatory response. These results reveal that hLF protects against A. actinomycetemcomitans bacteremia, as indicated by rapid bacterial clearance and decreased host proinflammatory mediators.
authors.affiliation: Rutgers School of Dental Medicine, Newark, New Jersey, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Velusamy
authors.forename: R
authors.initials: R
authors.lastname: Poojary
authors.forename: R
authors.initials: R
authors.lastname: Ardeshna
authors.forename: Waad
authors.initials: W
authors.lastname: Alabdulmohsen
authors.forename: D H
authors.initials: DH
authors.lastname: Fine
authors.forename: K
authors.initials: K
authors.lastname: Velliyagounder
mesh_terms: D000369:Aged, 80 and over; D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D000818:Animals; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology*; D002097:C-Reactive Protein / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007781:Lactoferrin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C552902:Ltf protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D002097:C-Reactive Protein; D052247:Nitric Oxide Synthase Type II; D007781:Lactoferrin