Lactoferrin protects neonatal rats from gut-related systemic infection

Lactoferrin is a milk protein that reportedly protects infants from gut-rel ated, systemic infection. Proof for this concept is limited and was address ed during in vivo and in vitro studies. Neonatal rats pretreated orally wit h recombinant human lactoferrin (rhLF) had less bacteremia and lower diseas e severity scores (P< 0.001) after intestinal infection with Escherichia co li. 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 c ontrol animals had a twofold increase in bacterial counts compared with cul tures from rh-LF-treated pups (P< 0.02). Oral therapy with rh-LF + FeSO4 di d not alter the protective effect. In vitro studies confirmed that rh-LF in teracted with the infecting bacterium and rat macrophages. An in vitro assa y showed that rh-LF did not kill E. coli, but a combination of rh-LF + lyso zyme was microbicidal. In vitro studies showed that rat macrophages release d escalating amounts of nitric oxide and tumor necrosis factor-alpha when s timulated with increasing concentrations of rh-LF. The in vitro studies sug gest that rh-LF may act with other "natural peptide antibiotics" or may pri me macrophages to kill E. coli in vivo.