Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin

Jpn J Cancer Res. 2000 Oct;91(10):1022-7. doi: 10.1111/j.1349-7006.2000.tb00880.x.

Abstract

We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly increases CD4(+) and CD8(+) T cells and NK (asialoGM1(+) ) cells in the blood of tumor-bearing mice and enhances anti-metastatic activity. In this paper, we document that oral administration of bLF and bLF-hydrolysate (bLFH) is associated with strong increases in CD4(+) and CD8(+) T, as well as asialoGM1(+) cells in lymphoid tissues and lamina propria of the small intestine in mice, especially in tumor-bearing animals in which Co26Lu cells were implanted subcutaneously. Moreover, IgM(+) and IgA(+) B cells in lamina propria of the small intestine were also significantly increased by bLF and bLFH. Bovine apo-transferrin (bTF) did not exhibit such activity. In the colon, only CD8(+) cells were significantly increased by treatment with bLF, while asialoGM1(+) cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1(+) cells. Administration of bLF and bLFH, but not bTF, increased production of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and caspase-1 in the mucosa of the small intestine. Particularly high levels of IL-18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, but not bTF, induced IFN-gamma presenting cells in the small intestine. Caspase-1, which processes proIL-18 to mature IL-18, was also induced in the epithelial cells of the small intestine following treatment with bLF and bLFH, but not with bTF. These results suggest that enhanced production of IL-18 and IFN-gamma and caspase-1 induction by treatment with bLF may be important for elevation of intestinal mucosal immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Caspase 1 / biosynthesis
  • Cattle
  • Immunity, Mucosal*
  • Interferon-gamma / biosynthesis
  • Interleukin-18 / biosynthesis
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestine, Large / drug effects
  • Intestine, Large / immunology
  • Intestine, Small / drug effects
  • Intestine, Small / immunology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lactoferrin / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / immunology*
  • Peptide Fragments / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Interleukin-18
  • Peptide Fragments
  • Interferon-gamma
  • Lactoferrin
  • Caspase 1