The Mode of Oral Bovine Lactoferrin Administration Influences Mucosal and Systemic Immune Responses in Mice

Abstract

Food protein intake interacts with the immune system. In earlier nutritional and immunological studies, nutrients, particularly milk whey proteins, were generally administered in soluble form and by gavage. However, orogastric intubation does not represent a natural way of ingesting nutrients such as lactoferrin (Lf). We examined how different modes of oral administration of Lf could affect the regulatory effect of this molecule on intestinal and systemic immune responses. Groups of 10 female BALB/c mice were administered Lf daily for 6 wk. To address the influence of the oral modes of administration, mice were given Lf either in solution, by gastric intubation or in the drinking water, or as a powder, by buccal deposition or in the diet. Mucosal and systemic immune responses, including specific immunoglobulin (Ig) secretion, cell proliferation, and cytokine production, were analyzed and compared with those of naïve mice given water under the same conditions or positive control mice that were administered Lf by i.m. injection. The addition of Lf to the drinking water had no visible effect on the immune status. Gastric intubation, single buccal doses, and continuous doses of Lf in the diet stimulated transient systemic and intestinal antibody responses against Lf. All of these oral modes of Lf exposure biased mucosal and systemic T-cell responses toward Thelper (Th)2-types and elevated IgA production by mucosal cells. However, the less natural gastric intubation also promoted Th1-type responses as evidenced by serum IgG(2a) antibodies and the secretion of Th1 cytokine by mucosal and systemic T cells in vitro. Thus, one should carefully consider the oral mode of administration for understanding regulation of immune responses by food proteins such as Lf.

Modulation of intestinal mucosal immunity by dietary polyunsaturated fatty acids in chickens

“…These findings suggest that fish oil increases the proportion of Th to promote acquired immunity, and that corn oil increases the proportion of CTL to improve cellular immunity of the GI tract. Several studies have indicated that CD8 T cells require CD4 T cells help for proliferation (Smith et al 2004). Combined with our results, corn oil increased the ratio of CTL, but reduced the ratio of Th.…”

“…Birds' IML were isolated by a modification of the method of Davis and Parrott (1981) and Sfeir et al (2004). The middle sections of jejunum were aseptically collected immediately after slaughter at d 21, and thoroughly washed with cold calcium and magnesium ion free Hanks' balanced salt solutions (CMF).…”

Modulation of Immunity-Related Gene Expression in Small Intestines of Mice by Oral Administration of Lactoferrin

“…In view of the fact that previous investigations showed that LF administration increases the numbers of some subsets of lymphocytes in the intestine (10,37), enhancement of CCR9 expression may have been due to an increase in the number of CCR9-expressing lymphocytes. It has been reported that after 1 week of oral administration of bovine LF, antigen-specific antibody and cytokine responses are induced (20). However, the effect of bovine LF observed here shortly after administration would not have been due to action as a foreign antigen.…”

Anti herpes simplex virus activity of lactoferrin/lactoferricin – an example of antiviral activity of antimicrobial protein/peptide

“…The antibacterial activity of Lf has been well reviewed against a broad spectrum of bacterial strains [65][66][67]. Several immunological functions have been ascribed to Lf, although their detailed mechanisms remain unknown [68][69][70][71][72][73]. Lf has also been shown to inhibit tumor growth [74], fungal infections [75][76] as well as viral infections [77][78][79][80][81][82][83][84][85][86][87][88][89].…”