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The Protective Effects of Lactoferrin Feeding against Endotoxin Lethal Shock in Germfree Piglets

Wang J. Lee,1, Jeffrey L. Farmer,2 Milo Hilty,3 and Yoon B. Kim1,*

Finch University of Health Sciences/The Chicago Medical School, North Chicago,1 and Abbott Laboratories, Abbott Park,2 Illinois 60064, and Ross Laboratories, Columbus, Ohio 432153

Received 10 November 1997/Returned for modification 22 December 1997/Accepted 15 January 1998

The unique germfree, colostrum-deprived, immunologically "virgin" piglet model was used to evaluate the ability of lactoferrin (LF) to protect against lethal shock induced by intravenously administered endotoxin. Piglets were fed LF or bovine serum albumin (BSA) prior to challenge with intravenous Escherichia coli lipopolysaccharide (LPS), and temperature, clinical symptoms, and mortality were tracked for 48 h following LPS administration. Prefeeding with LF resulted in a significant decrease in piglet mortality compared to feeding with BSA (16.7 versus 73.7% mortality, P < 0.001). Protection against the LPS challenge by LF was also correlated with both resistance to induction of hypothermia 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 binding to monocytes/macrophages and, in turn, prevention of induction of monocyte/macrophage-derived inflammatory-toxic cytokines.

Infect. Immun., 12 1995, 4917-4920, Vol 63, No. 12

Copyright © 1995, American Society for Microbiology