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Am J Physiol Gastrointest Liver Physiol 281: G1140-G1150, 2001;
0193-1857/01 $5.00
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Vol. 281, Issue 5, G1140-G1150, November 2001

TRANSLATIONAL PHYSIOLOGY
Lactoferrin protects neonatal rats from gut-related systemic infection

Lynn Edde1,5,*, Ronaldo B. Hipolito2,*, Freda F. Y. Hwang2, Denis R. Headon3, Robert A. Shalwitz4, and Michael P. Sherman2,5

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-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.

bacteremia; Escherichia coli; disease severity score; human lysozyme; macrophage-related priming or activation; recombinant human lactoferrin

* L. Edde and R. B. Hipolito contributed equally to this investigation.




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