title: Lactoferrin protects neonatal rats from gut-related systemic infection.
abstract: Lactoferrin is a milk protein that reportedly protects infants from gut-related, systemic infection. Proof for this concept is limited and was addressed during in vivo and in vitro studies. Neonatal rats pretreated orally with recombinant human lactoferrin (rh-LF) had less bacteremia and lower disease severity scores (P < 0.001) after intestinal infection with Escherichia coli. Control animals had 1,000-fold more colony-forming units of E. coli per milliliter of blood than treated animals (P < 0.001). Liver cultures from control animals had a twofold increase in bacterial counts compared with cultures from rh-LF-treated pups (P < 0.02). Oral therapy with rh-LF + FeSO(4) did not alter the protective effect. In vitro studies confirmed that rh-LF interacted with the infecting bacterium and rat macrophages. An in vitro assay showed that rh-LF did not kill E. coli, but a combination of rh-LF + lysozyme was microbicidal. In vitro studies showed that rat macrophages released escalating amounts of nitric oxide and tumor necrosis factor-alpha when stimulated with increasing concentrations of rh-LF. The in vitro studies suggest that rh-LF may act with other "natural peptide antibiotics" or may prime macrophages to kill E. coli in vivo.
authors.affiliation: Department of Pediatrics, University of Arizona, Tucson, 85724, USA.
authors.forename: L
authors.initials: L
authors.lastname: Edde
authors.forename: R B
authors.initials: RB
authors.lastname: Hipolito
authors.forename: F F
authors.initials: FF
authors.lastname: Hwang
authors.forename: D R
authors.initials: DR
authors.lastname: Headon
authors.forename: R A
authors.initials: RA
authors.lastname: Shalwitz
authors.forename: M P
authors.initials: MP
authors.lastname: Sherman
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D016923:Cell Death; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000378:metabolism; D004338:Drug Combinations; D051766:Early Growth Response Protein 1; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D004927:Escherichia coli Infections / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins; D007422:Intestines / Q000382:microbiology*; D007781:Lactoferrin / Q000494:pharmacology*; D008099:Liver / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009113:Muramidase / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004338:Drug Combinations; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D009113:Muramidase; D007781:Lactoferrin