Lactoferrin protects rabbits from Shigella flexneri-induced inflammatory enteritis

Abstract

Shigella species cause bacillary dysentery in humans by invasion, intracellular multiplication, spread to adjacent cells, and induction of brisk inflammatory responses in the intestinal epithelium. In vitro data suggest that lactoferrin, a glycoprotein present in human mucosal secretions, has a role in protection from bacterial enteric infections. We sought to determine the activity of lactoferrin in vivo, using the concentration present in human colostrum, to investigate its effect on the development of clinical and pathological evidence of inflammation in a rabbit model of enteritis. Lactoferrin protected rabbits infected with Shigella flexneri from developing inflammatory intestinal disease. Typical histological changes in ill animals included villous blunting with sloughing of epithelial cells, submucosal edema, infiltration of leukocytes, venous congestion, and hemorrhage. Lactoferrin at a concentration normally found in human colostrum blocks development of S. flexneri-induced inflammatory enteritis.

FIG. 1.

Macroscopic evidence of severe inflammatory enteritis in a portion of ileum of a rabbit infected with Shigella and not receiving lactoferrin treatment (bottom). Normal distal ileum in an infected animal treated with lactoferrin (top).

FIG. 2.

The bottom left panel shows the normal histological appearance of a section of ileum of a rabbit infected with Shigella and receiving lactoferrin treatment. (score, 0) The other panels show typical histological changes in a section of ileum of ill rabbits infected with Shigella and not receiving lactoferrin treatment (right top, low-power magnification; bottom, high-power magnification) (score 5) showing blunting of villi, submucosal edema, hemorrhages, and severe inflammation.