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