title: Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan. j_togawa@med.yokohama-cu.ac.jp
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Togawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Nagase
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inamori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: Norio
authors.initials: N
authors.lastname: Ueno
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Saito
authors.forename: Hisahiko
authors.initials: H
authors.lastname: Sekihara
mesh_terms: 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
chemical_list: D016207:Cytokines; D016264:Dextran Sulfate; D009195:Peroxidase; D007781:Lactoferrin