THE PROTECTIVE EFFECTS OF LACTOFERRIN FEEDING AGAINST ENDOTOXIN LETHAL SHOCK IN GERM-FREE PIGLETS

The unique germfree, colostrum-deprived, immunologically ''virgin'' pi glet model was used to evaluate the ability of lactoferrin (LF) to pro tect against lethal shock induced by intravenously administered endoto xin. Piglets were fed LF or bovine serum albumin (BSA) prior to challe nge with intravenous Escherichia coli lipopolysaccharide (LPS), and te mperature, clinical symptoms, and mortality were tracked for 48 h foll owing LPS administration. Prefeeding with LF resulted in a significant decrease in piglet mortality compared to feeding with BSA (16.7 versu s 73.7% mortality, P < 0.001). Protection against the LPS challenge by LF was also correlated with both resistance to induction of hypotherm ia by endotoxin and an overall increase in wellness, as quantified by a toxicity score developed for these studies. In vitro studies using a flow cytometric assay system demonstrated that LPS binding to porcine monocytes was inhibited by LF in a dose-dependent fashion, suggesting that the mechanism of LF action in vivo may be inhibition of LPS bind ing to monocytes/macrophages and, in turn, prevention of induction of monocyte/macrophage-derived inflammatory-toxic cytokines.