Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance.
OBJECTIVE
The natural immunomodulator, lactoferrin, is widespread among various biological fluids and is known to exert an anti-inflammatory effect. However, there has been only one study that examined the mode of action of lactoferrin in reducing intestinal damage. We investigated the therapeutic role of lactoferrin and its effect on the levels of pro-inflammatory and anti-inflammatory cytokines, by using a rat model of dextran sulfate sodium (DSS) induced-colitis.


METHODS
Male Sprague-Dawley rats were given distilled drinking water containing 2.5% (wt/vol) synthetic DSS ad libitum. Bovine lactoferrin was given once daily through gavage, starting 3 days before beginning the DSS administration, until death. The whole colon was removed to be examined macroscopically and histologically. Myeloperoxidase activity, and pro-inflammatory and anti-inflammatory cytokines in the colonic tissue were also measured.


RESULTS
Dextran sulfate sodium-induced colitis was attenuated by oral administration of lactoferrin in a dose-dependent manner, as reflected by improvement in clinical disease activity index, white blood cell count and hemoglobin concentration, macroscopic and histological scores, and myeloperoxidase activity. Reduced inflammation in response to lactoferrin was correlated with the significant induction of the anti-inflammatory cytokines, interleukin-4 and interleukin-10, and with significant reductions in the pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1beta, and interleukin-6.


CONCLUSIONS
We concluded that oral administration of lactoferrin exerts a protective effect against the development of colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.
Togawa
Jun-Ichi
J
Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan. j_togawa@med.yokohama-cu.ac.jp
Nagase
Hajime
H
Tanaka
Katsuaki
K
Inamori
Masahiko
M
Nakajima
Atsushi
A
Ueno
Norio
N
Saito
Toshifumi
T
Sekihara
Hisahiko
H
D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004305:Dose-Response Relationship, Drug; D007781:Lactoferrin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D016264:Dextran Sulfate; D009195:Peroxidase; D007781:Lactoferrin