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1 Department of Pediatrics, University of Arizona, Tucson, Arizona 85724; 2 Department of Pediatrics, University of California, Davis, California 95616; 3 Agennix Incorporated, Houston, Texas 77046; 4 Ross Products Division, Abbott Laboratories, Columbus, Ohio 43215; and 5 Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030
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 + FeSO4 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-
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.
bacteremia; Escherichia coli; disease severity score; human lysozyme; macrophage-related priming or activation; recombinant human lactoferrin
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