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

We have previously demonstrated that oral administration of bovine lactofer rin (bLF) markedly increases CD4(+) and CDS+ T cells and NK (asialoGM1(+)) cells in the blood of tumor-bearing mice and enhances anti-metastatic activ ity. In this paper, we document that oral administration of bLF and bLF-hyd rolysate (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 Co26 Lu 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 activit y, In the colon, only CD8(+) cells were significantly increased by treatmen t with bLF, while asialoGM1(+) cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1(+) cells. Administrat ion of bLF and bLFH, but not bTF, increased production of interleukin-18 (I L-18), interferon-gamma (IFN-gamma) and caspase-1 in the mucosa of the smal l intestine. Particularly high levels of IL-18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, bu t not bTF, induced IFN-gamma presenting cells in the small intestine. Caspa se-1, which processes proIL-18 to mature IL-18, was also induced in the epi thelial 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 importan t for elevation of intestinal mucosal immunity.