Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin.
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.
Wang
W P
WP
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Iigo
M
M
Sato
J
J
Sekine
K
K
Adachi
I
I
Tsuda
H
H
D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D020170:Caspase 1 / Q000096:biosynthesis; D002417:Cattle; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D007420:Intestine, Large / Q000187:drug effects / Q000276:immunology; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D020382:Interleukin-18; D010446:Peptide Fragments; D007371:Interferon-gamma; D007781:Lactoferrin; D020170:Caspase 1