Protective Proteins in Mammalian Milks

Abstract

and Niklas have disclosed no financial relationships relevant to this article. This commentary does contain a discussion of an unapproved/ investigative use of a commercial product/ device. Educational Gaps1. In clinical trials, lactoferrin (LF) shows promise for reducing mortality and preventing neonatal infections, particularly late-onset sepsis and necrotizing enterocolitis. 2. Until the U.S. Food and Drug Administration approves of LF-containing preparations to ward off neonatal infection, colostrum feeding should be encouraged for preterm infants as soon as possible after birth because of its high LF concentrations. AbstractHuman milk is the ideal nutrient for neonates. Breastfeeding exposes neonates to maternal microflora, provides host protection, and has proteins that mediate immune system development. Lactoferrin (LF) is the major whey protein in mammalian milk, and its multifunctional characteristics have shown importance in preventing infections. Ferric iron binding and natural peptide antibiotic properties of LF likely promote a healthy intestinal microbiome that prevents bacterial translocation and mediates optimal epithelial growth and differentiation. An established asset of LF is stimulation of naïve dendritic cells; this initiates the emergence of neonatal Th1 helper cells, thereby reversing the Th2 bias associated with pregnancy. Moreover, LF promotes development of Peyer patches, which leads to enhanced IgA secretion into the intestinal lumen. The anti-inflammatory properties of LF involve its binding of endotoxin and other proinflammatory molecules released by intestinal pathogens. LF also blocks receptors that microbes use for epithelial invasion, and thus LF mitigates a proinflammatory response by the host during infection. These properties of LF are known from basic science research and preclinical investigations, and they have resulted in the enteral use of bovine and recombinant human LF to prevent neonatal late onset sepsis. Bovine LF has been shown to reduce the incidence of late onset sepsis in extremely preterm infants, but Food and Drug Administration approval of LF for use in the NICU has not taken place. Because LF is currently available only for scientific investigations, the feeding of a mother's milk is encouraged shortly after birth because the concentration of LF is highest in colostrum.

Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants

“…We proposed TLf might reduce inflammation in treated infants. 9 The peak C-reactive protein level was not different between infants fed TLf (n = 30) vs placebo (n = 38) (1.6 ± 1.6 mg/dL vs 2.8 ± 6.0 mg/, respectively).…”

“…We propose that the human milk protein lactoferrin partly explains these beneficial effects. 9,10 Commercial recombinant human lactoferrin became available 20 years ago. 11 We found feeding TLf prophylactically to neonatal rats prevented morbidity and mortality caused by enteroinvasive Escherichia coli .…”

Neonatal Vaccination: Challenges and Intervention Strategies

“…Newer adjuvants should aim to boost vaccine responses by activating innate immune signaling pathways as BCG does. Lactoferrin, a major whey protein component of milk, has been shown to promote dendritic cells maturation and IL-12 production in neonatal mice model of influenza, and can be considered as a safe adjuvant [42,43]. In addition to processing antigen into a form recognizable by lymphocytes, APCs also express diverse cytokines and costimulatory molecules which can profoundly influence the course of an immune response [44,45].…”

Lactoferrin and necrotizing enterocolitis

“…4 Figure 1 reviews the wide range of actions attributed to LF. The ways that LF prevent NEC include: a) its role in host defense against pathogens, 17,18 b) its immuno-modulatory and anti-inflammatory effects, 12,16,19,20 c) its regulation of intestinal cell growth, 9,21,22 and d) its biochemical actions that include ferric iron transport, 23,24 enzymatic activity, 25,26 and nuclear binding and initiation of transcription. 18,27,28 The pathophysiology of NEC is complex, but several factors are accepted as effectors of the disease.…”

“…The remainder of this section will present in greater depth, specific actions of LF that are responsible for diminishing the risk of NEC in preterm infants. 20,35,37 These actions are vital to host defense against pathogens, but the effect is also anti-inflammatory (Fig. 2).…”