Other Defense Factors In Milk Acting In The Infants

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It is unknown whether or not the limited amounts of IgG and IgM antibodies present in the maternal milk play a measureable role in the mucosal defense of the infant.

In early colostrum the major milk protein is SIgA, in mature milk it is lactoferrin (LF) at the level of2-5 g/15LF is a single chain glycoprotein. Its peptide chain contains 692 aminoacids and folds into two globular lobes; each ofthese contains an iron-binding site18. LF has many functions besides binding iron. It is bacteriostatic and bactericidal for many species. It also inhibits certain viruses, kills yeasts and even certain tumour cells in vitro18 19. Enzymic degradation gives rise to peptides, especially the lactoferricin (LF-cin), which are efficientlybactericidal20.

LF and LF-cin are also anti-inflammatory, e.g. by inhibiting production of anti-inflammatory cytokines like IL-1, IL-6, IL-8, TNF-a 18-21-22. Furthermore, it can bind to B-cells and inhibit antibody synthesis, affect T cell proliferation, interfere with the complement system, interfere with the cytotoxic effects ofNK cells and block histamin release from mast cells22-

There are data to suggest that LF and LF peptides come out in the urine of preterm breastfed infants2526. Milk SIgA antibodies coat the enteric bacteria which are usually the cause of urinary tract infections by entering the urinary tract from below. The anti-adherence effects of these antibodies may help preventing such a course. Breastfed infants also have a higher level of oligosaccharide receptor analogues in the urine thannon-breastfed27-29. Furthermore, breastfeeding may result in a selection of less virulent bacteria in the gut 30-32. All these factors may help explaining how breastfeeding can protect against urinary tract infections33'34.

We have studied the possible protective role of orally given human LF and LF peptides against urinary tract infections caused by E. coli in the mouse35 .The LF structures were given 30 minutes after the introduction of the bacteria into the urinary tract. The LF reduced the number ofbacteria in the bladder and the kidneys compared to the control 24 hours after the start of the infection (p<0.0001 and p=0.006). One of the peptides also reduced the number ofbacteria in the kidneys. The LF could reduce the levels ofthe inflammatogenic IL-6 both in the urine and the blood (p<0.05 and p<0.02). Thus it seems that milk LF may reach the urinary tract presumably after binding to the LF receptors in the intestinal brush-border23. Such a transport may also involve some of the peptides resulting from enzymic degradation ofthe relatively resistant LF in the gut.

Using experimental colitis in mice as another in vivo model we could also show protective effects of LF36 .Thus there were significant effects delaying the appearance ofblood in the stool (p<0.001) and macroscopic bleedings from the rectum (p=0.008). The length ofthe colon was not reduced in the LF treated group as in the untreated controls (p<0.05) and there were fewer changes in the histologic picture (p=0.012). Synthetic peptides derived from LF seemed also able to reduce the inflammatory changes including the number ofMHC II positive cells. High levels of LF could be shown in serum and also in urine ofthe LF-treated animals. Thus it may be that LF provided via breastfeeding may have an anti-inflammatory activity in the gut.

Most of the anti-viral effects of milk seem to be connected with LF, although there are also SIgA antibodies to viruses like parainfluenzae, influenzae A, rhinovirus, rotavirus, poliovirus, cytomegalovirus and respiratory syncytial virus. Why breastfeeding, which protects so well against many other enteric infections, does not provide more than a delaying or partial defense against rotavirus infections is not quite clear37-39.

The lactadherin which is a 46kDa mucinrelated glycoprotein can bind rotavirus and seemed to be protective in a study of rotavirus infections in Mexican children40.This has been debated41.

There are several other protective components in human milk than antibodies and LF, but their protective capacity need further studies. This is true for the 90K, Mac2 binding protein in milk, which has been claimed to protect against viral infections in the respiratory tract42 Its possible effect on enteric viruses does not seem to have been studied.

The presence of leptin in the milk43 may be of significance for the infant's host defense since leptin has the structure and several functions of a cytokine44,45.It stimulates haematopoeitic and lymphoid cells, especially TH1 cells which produce IFN-y it enhances phagocytosis and may upregulate inflammatory cytokines45 However, the role of milk leptin for the offspring has not yet been investigated, when it comes to its possible role for the immune system.

Certain bacterial enterotoxins induce a regulatory peptide, anti-secretory factor (AF), which turns off diarrhoea46. A structurally closely related group ofpeptides called feed-induced lectins (FIL) reduces the prevalence ofpost-weaning diarrhoea in piglets47. A proper mix of sugars and aminoacids, or processed cereals can induce FIL. With such a diet we were recently finally able to control devastatingly voluminous and frequent diarrhoeas in a patient with hypogammaglobulinemia on immunoglobulin prophylaxis, but without AF in his intestinal mucosa.

Furthermore, using Western blot we have been able to demonstrate the presence of AFFIL in milk from Pakistani and Guatemalan mothers, but not from Swedish mothers 48.Presumably the Swedish mothers had not been exposed to microbial enterotoxins as the other mothers presumably had. It is possible that the presence of AF/FIL in maternal milk can be yet another factor which protects against diarrhoeal disease in the offspring. We do not know whether it is possible to induce AFFIL in the milk via the mother's diet.

There are numerous cytokines and growth factors present in human milk49-51. Especially IFN- y, TGF-P (Transforming Growth Factor- P) and G-CSF (Granulocyte-Colony Stimulating Factor) are present in high amounts in milk. These components may well be functional in the infant. This is suggested for TGF- pi by the fact that fosterfeeding rescued gene-disrupted newborn mice to early survival and normal development52.

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New Mothers Guide to Breast Feeding

New Mothers Guide to Breast Feeding

For many years, scientists have been playing out the ingredients that make breast milk the perfect food for babies. They've discovered to day over 200 close compounds to fight infection, help the immune system mature, aid in digestion, and support brain growth - nature made properties that science simply cannot copy. The important long term benefits of breast feeding include reduced risk of asthma, allergies, obesity, and some forms of childhood cancer. The more that scientists continue to learn, the better breast milk looks.

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