title: Inhibition of intestinal polyp growth by oral ingestion of bovine lactoferrin and immune cells in the large intestine.
abstract: Studies using animal models have demonstrated that ingestion of bovine lactoferrin (bLF) inhibits carcinogenesis in the colon and other organs of experimental animals. As a result of these studies, a blinded, randomized, controlled clinical trial was conducted in the National Cancer Center Hospital, Tokyo, Japan to determine whether ingestion of bLF had an effect on the growth of colorectal polyps in humans. Patients with colorectal polyps ≤5 mm diameter and likely to be adenomas ingested 0, 1.5, or 3.0 g bLF daily for 1 year. Ingestion of 3.0 g bLF suppressed the growth of colorectal polyps and increased the level of serum human lactoferrin in trial participants 63 years old or younger. The purpose of the present study was to investigate correlations between immune parameters and changes in polyp size. Trial participants with regressing polyps had increased NK cell activity, increased serum hLF levels (indicating increased neutrophil activity), and increased numbers of CD4+ cells in the polyps. These findings are consistent with a correlation between higher immune activity and suppression of colorectal polyps. In addition, participants with regressing polyps had lower numbers of PMNs and increased numbers of S100A8+ cells in the polyps, consistent with a correlation between lower inflammatory potential in the colon and suppression of colorectal polyps. Trial participants ingesting bLF had increased serum hLF levels, a possible increase in systemic NK cell activity, and increased numbers of CD4+ and CD161+ cells in the polyps. Taken together, our findings suggest that bLF suppressed colorectal polyps by enhancing immune responsiveness.
authors.affiliation: Nanotoxicology Project, Nagoya City University, Nagoya, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iigo
authors.forename: David B
authors.initials: DB
authors.lastname: Alexander
authors.forename: Jiegou
authors.initials: J
authors.lastname: Xu
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Futakuchi
authors.forename: Masumi
authors.initials: M
authors.lastname: Suzui
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kozu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Akasu
authors.forename: Daizo
authors.initials: D
authors.lastname: Saito
authors.forename: Tadao
authors.initials: T
authors.lastname: Kakizoe
authors.forename: Koji
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Abe
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Takase
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sekine
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007417:Intestinal Polyps / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007420:Intestine, Large / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D007781:Lactoferrin / Q000008:administration & dosage* / Q000097:blood; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology
chemical_list: D015703:Antigens, CD; C504120:CEACAM8 protein, human; D040501:Calgranulin A; D040502:Calgranulin B; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007781:Lactoferrin