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
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