Lactoferrin in Human Milk of Prolonged Lactation.

Among the immunologically important bioactive factors present in human milk, lactoferrin (Lf) has emerged as a key player with wide-ranging features that directly and indirectly protect the neonate against infection caused by a variety of pathogens. The concentration of Lf in human milk is lactation-stage related; colostrum contains more than 5 g/L, which then significantly decreases to 2-3 g/L in mature milk. The milk of mothers who are breastfeeding for more than one year is of a standard value, containing macronutrients in a composition similar to that of human milk at later stages. The aim of this study was to evaluate lactoferrin concentration in prolonged lactation from the first to the 48th month postpartum. Lactating women (n = 120) up to 48 months postpartum were recruited to the study. The mean value of lactoferrin concentration was the lowest in the group of 1-12 months of lactation (3.39 ± 1.43 g/L), significantly increasing in the 13-18 months group (5.55 ± 4.00 g/L; p < 0.006), and remaining at a comparable level in the groups of 19-24 month and over 24 months (5.02 ± 2.97 and 4.90 ± 3.18 g/L, respectively). The concentration of lactoferrin in mother's milk also showed a positive correlation with protein concentration over lactation from the first to the 48th month (r = 0.3374; p = 0.0002). Our results demonstrate the high immunology potential of human milk during prolonged lactation and that Lf concentration is close to the Lf concentration in colostrum. Evidence of stable or rising immunoprotein levels during prolonged lactation provides an argument for foregoing weaning; however, breastfeeding must be combined with solid foods meet the new requirements of a rapidly growing six-month or older baby.

Effect of the Zn Supplementation on Immuno-Modulatory Activities of Bovine Lactoferrin in the Murine Splenocytes and RAW264.7 Macrophages.

Lactoferrin (LF) has important bio-functions including immuno-modulation, while essential trace metals may interact with LF and thereby induce property especially bio-activity changes. Bovine LF was thus supplemented with Zn2+ at 0.16, 0.32, and 0.64 mg/g LF to yield 10%, 20%, and 40% Zn-saturation, respectively. Afterwards, bovine LF and the Zn-supplemented LF products at 10-40-µg/mL doses were compared for their immuno-modulatory activities in two immune cells (murine splenocytes and RAW264.7 macrophages), using the stimulation index of the splenocytes, T lymphocyte subpopulations, macrophage phagocytosis, and cytokine production as evaluation reflectors. The results showed that bovine LF and the Zn-supplemented LF products had suppressive effect on the splenocytes and concanavalin A (ConA)- and lipopolysaccharide-stimulated splenocytes, but lower Zn-saturation and lower dose could alleviate and even counteract this suppressive effect (P < 0.05). More importantly, the Zn-supplemented LF product with lower Zn-saturation at lower dose exerted slightly higher macrophage stimulation, increased CD4+/CD8+ ratio of T lymphocyte subpopulations, and were capable of enhancing the interleukin-2 (IL-2), IL-4, and interferon-γ production in the splenocytes or the IL-1ß, IL-6, and tumor necrosis factor-α production in the macrophages significantly (P < 0.05). Contrary to its counterpart at lower dose, the Zn-supplemented LF product with higher Zn-saturation at higher dose mostly showed opposite effects in the two cell models. It is concluded that Zn supplementation has an impact on the immuno-modulation of bovine LF, while Zn-saturation is a key factor to modulate these assessed immune activities.

Lactoferrin: A Critical Player in Neonatal Host Defense.

Newborn infants are at a high risk for infection due to an under-developed immune system, and human milk has been shown to exhibit substantial anti-infective properties that serve to bolster neonatal defenses against multiple infections. Lactoferrin is the dominant whey protein in human milk and has been demonstrated to perform a wide array of antimicrobial and immunomodulatory functions and play a critical role in protecting the newborn infant from infection. This review summarizes data describing the structure and important functions performed by lactoferrin in protecting the neonate from infection and contributing to the maturation of the newborn innate and adaptive immune systems. We also briefly discuss clinical trials examining the utility of lactoferrin supplementation in the prevention of sepsis and necrotizing enterocolitis in newborn infants. The data reviewed provide rationale for the continuation of studies to examine the effects of lactoferrin administration on the prevention of sepsis in the neonate.

Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products.

Diarrhea is a common illness among travelers to resource-limited countries, the most prevalent attributable agent being enterotoxigenic Escherichia coli (ETEC). At this time, there are no vaccines licensed specifically for the prevention of ETEC-induced traveler's diarrhea (TD), and this has propelled investigation of alternative preventive methods. Colostrum, the first milk expressed after birthing, is rich in immunoglobulins and innate immune components for protection of newborns against infectious agents. Hyperimmune bovine colostrum (HBC) produced by immunization of cows during gestation (and containing high levels of specific antibodies) is a practical and effective prophylactic tool against gastrointestinal illnesses. A commercial HBC product, Travelan, is available for prevention of ETEC-induced diarrhea. Despite its demonstrated clinical efficacy, the underlying immune components and antimicrobial activity that contribute to protection remain undefined. We investigated innate and adaptive immune components of several commercial HBC products formulated to reduce the risk of ETEC-induced diarrhea, including Travelan and IMM-124E, a newer product that has broader gastrointestinal health benefits. The immune components measured included total and ETEC-specific IgG, total IgA, cytokines, growth factors, and lactoferrin. HBC products contained high levels of IgG specific for multiple ETEC antigens, including O-polysaccharide 78 and colonization factor antigen I (CFA/I) present in the administered vaccines. Antimicrobial activity was measured in vitro using novel functional assays. HBC greatly reduced ETEC motility in soft agar and exhibited bactericidal activity in the presence of complement. We have identified immune components and antimicrobial activity potentially involved in the prevention of ETEC infection by HBC in vivo.

Lactoferrin and necrotizing enterocolitis.

PURPOSE OF REVIEW: There is an intense interest among neonatal caregivers as to whether lactoferrin given enterally may reduce the incidence of necrotizing enterocolitis in preterm infants. This review presents scientific and clinical evidence that lactoferrin alleviates or prevents this life-threatening disease. RECENT FINDINGS: Preclinical studies in neonatal rats showed that lactoferrin given orally before enteral infection with pathogenic Escherichia coli reduced bacteremia and mortality. A multicentered clinical trial found that very low-birth weight preterm infants given bovine lactoferrin had a significant reduction in late-onset sepsis; there was also a trend towards a diminished incidence of necrotizing enterocolitis. Although multicentered trials of lactoferrin use in preterm infants are near completion, regulatory burdens required to bring lactoferrin to the bedside may limit its availability. SUMMARY: Extremely preterm infants should receive colostrum, a natural lactoferrin concentrate, immediately after birth and, ideally, continue on breast milk throughout the hospital stay. This practice appears well tolerated, but additional experience will tell us whether this practice reduces the prevalence of necrotizing enterocolitis.

Lactoferrin and necrotizing enterocolitis.

Lactoferrin (LF) is a multifunctional protein and a member of the transferrin family. LF and lysozyme in breast milk kill bacteria. In the stomach, pepsin digests and releases a potent peptide antibiotic called lactoferricin from native LF. The antimicrobial characteristics of LF may facilitate a healthy intestinal microbiome. LF is the major whey in human milk; its highest concentration is in colostrum. This fact highlights early feeding of colostrum and also fresh mature milk as a way to prevent necrotizing enterocolitis.

Differential immunogenicity and allergenicity of native and recombinant human lactoferrins: role of glycosylation.

Human native milk lactoferrin (LF) and recombinant forms of lactoferrin (rLF) are available with identical aa sequences, but different glycosylation patterns. Native lactoferrin (NLF) possesses the intrinsic ability to stimulate vigorous IgG and IgE antibody responses in BALB/c mice, whereas recombinant forms (Aspergillus or rice) are 40-fold less immunogenic and 200-fold less allergenic. Such differences are independent of endotoxin or iron content and the glycans do not contribute to epitope formation. A complex glycoprofile is observed for NLF, including sialic acid, fucose, mannose, and Lewis (Le)(x) structures, whereas both rLF species display a simpler glycoprofile rich in mannose. Although Le(x) type sugars play a Th2-type adjuvant role, endogenous expression of Le(x) on NLF did not completely account for the more vigorous IgE responses it provoked. Furthermore, coadminstration of rLF downregulated IgE and upregulated IgG2a antibody responses provoked by NLF, but was without effect on responses to unrelated peanut and chicken egg allergens. These results suggest glycans on rLF impact the induction phase to selectively inhibit IgE responses and that differential glycosylation patterns may impact on antigen uptake, processing and/or presentation, and the balance between Th1 and Th2 responses.

Influence of oral lactoferrin on Mycobacterium tuberculosis induced immunopathology.

The ability of lactoferrin to provide protection and decrease immunopathology in infectious diseases was evaluated using an aggressive aerosol model of Mycobacterium tuberculosis (MTB) infection. C57BL/6 mice were challenged with MTB strain Erdman and treated with 0.5% bovine lactoferrin added to the drinking water starting at day 0 or day 7 post-infection. Mice were sacrificed at three weeks post-challenge and evaluated for organ bacterial burden, lung histopathology, and ELISpot analysis of the lung and spleen for immune cell phenotypes. Mice given tap water alone had lung log10 colony forming units (CFUs) of 7.5 ± 0.3 at week 3 post-infection. Lung CFUs were significantly decreased in mice given lactoferrin starting the day of infection (6.4 ± 0.7), as well as in mice started therapeutically on lactoferrin at day 7 after established infection (6.5 ± 0.4). Quantitative immunohistochemistry using multispectral imaging demonstrated that lung inflammation was significantly reduced in both groups of lactoferrin treated mice, with decreased foamy macrophages, increased total lymphocytes, and increased numbers of CD4+ and CD8+ cells. ELISpot analysis showed that lactoferrin treated mice had increased numbers of CD4 + IFN-γ+ and IL-17 producing cells in the lung, cells that have protective functions during MTB infection. Lactoferrin alone did not alter the proliferation of MTB in either broth or macrophage culture, but enhanced IFN-γ mediated MTB killing by macrophages in a nitric oxide dependent manner. These studies indicate that lactoferrin may be a novel therapeutic for the treatment of tuberculosis, and may be useful in infectious diseases to reduced immune-mediated tissue damage.

Comparing efficacy of BCG/lactoferrin primary vaccination versus booster regimen.

Lactoferrin is an iron binding glycoprotein possessing multiple immune modulatory activities, including ability to affect macrophage cytokine production, promote maturation of T- and B-lymphocyte and immature dendritic cells, and enhance the ability of macrophages and dendritic cells to stimulate antigen-specific T-cells. These characteristics of lactoferrin suggested that it could function as an effective adjuvant enhance efficacy of the BCG, the current vaccine for tuberculosis disease. Admix of lactoferrin to the BCG vaccine promoted host protective responses that surpasses activity of the BCG vaccine alone as determined by decreasing pulmonary pathology upon challenge with virulent Mycobacterium tuberculosis (MTB). This study builds on previous reports by examining the effectiveness of the lactoferrin adjuvant comparing primary vaccination versus an immunization schedule with a booster administered at 8 weeks. BCG/lactoferrin vaccinating, given once or twice, demonstrated an improvement in pulmonary disease compared to both the BCG vaccinated and non-immunized groups. The splenic recall profiles showed a difference in cytokine production induced by mycobacterial antigen from splenocytes isolated from mice immunized with BCG/lactoferrin once or twice. Production of IL-17 is increased in the BCG/lactoferrin 2× group compared to the primary vaccinated group. Both BCG/lactoferrin vaccinated group exhibited increase production of IFN-γ compared to the non-immunized group and decreased production of IL-10 compared to the group vaccinated with only BCG. This study illustrates that the adjuvant activity of lactoferrin to enhance BCG efficacy occurs whether the vaccination regimen is a single delivery or combined with a booster, leading to enhanced host protection and decreased disease manifestation.

Biological effects of novel bovine milk fractions.

Novel dairy fractions have been isolated and are now commercially available. Several of them have been shown to have biological activities in various test systems. α-Lactalbumin was first isolated to provide a good source of tryptophan, often the first limiting amino acid in infant formulas, but has then been shown to be digested into smaller peptides with antimicrobial and prebiotic activities, immunostimulatory effect and acting as enhancers of mineral absorption. Lactoferrin bioactivities include antibacterial and antiviral effects, regulation of immune function, stimulation of intestinal proliferation and differentiation and facilitating iron absorption, but these activities may have been limited due to earlier contamination with LPS. Lactoferrin free of lipopolysaccharide may prove to be more effective with regard to exerting these activities. Osteopontin is a heavily phosphorylated and glycosylated protein that modulates immune function and stimulates Th1/Th2 switching, and, possibly, also affects bone mineralization and growth. Biological activities of lactoferrin may be facilitated by osteopontin. Milk fat globule membranes are a fraction that has previously been excluded from infant formulas, but components of this fraction have been shown to exhibit antimicrobial activities and to prevent infection. Further clinical studies are needed on infants fed formulas with these components incorporated.

Lactoferrin: an iron-binding antimicrobial protein against Escherichia coli infection.

Escherichia coli (E. coli) are the most common aerobic gram-negative bacilli in a normal intestinal tract. They cause most of the intra-abdominal infections, wound infections associated with abdominal surgery, and septicemia. Most of these infections are of endogenous intestinal origin. Lactoferrin (LF) is an iron-binding glycoprotein found in milk and various external secretions. This protein has been found to have a number of biological functions, including antimicrobial, anti-cancer, antioxidant, and immunomodulatory effects. Partial degradation of LF by pepsin can give rise to peptides termed lactoferricin (LFcin) with more potent antimicrobial activity. LF and LFcin have been shown to inhibit the growth of a number of pathogenic bacteria (including E. coli and antibiotic-resistant strains), fungi, and even viruses in both in vitro and in vivo studies. We previously demonstrated that both recombinant porcine LF (pLF) produced from yeast and a synthetic 20-residue porcine LFcin peptide exhibit antimicrobial activity in vitro. In one of our recent studies, we performed pathogen challenges, including pathogenic E. coli, Staphylococcus aureus and Candida albicans, of the digestive tract of a transgenic milk-fed animal model. The results showed that LF has broad spectrum antimicrobial activity in the digestive tract and protects the mucosa of the small intestine from injury. Our following study also revealed that pLF as a feedstuff additive enhances avian immunity, including antibody formation and cell-mediated immunity. All of these results suggest that LF could be a novel natural protein in the treatment and prevention of infections with E. coli or antibiotic-resistant bacteria strains.

Bovine colostrum modulates immune activation cascades in human peripheral blood mononuclear cells in vitro.

Bovine colostrum (BC) is the thick yellow fluid a lactating cow gives to a suckling calf during its first days of life to support the growth of the calf and prevent gastrointestinal infections until the calf has synthesized its own active immune defense system. BC contains a complex system of immune factors and has a long history of use in traditional medicine. In an approach to evaluate the effects of bovine colostrum (BC) on the T-cell/macrophage interplay, we investigated and compared the capacity of BC containing low and high amounts of lactose and lactoferrin to modulate tryptophan degradation and neopterin formation in unstimulated and mitogen-stimulated human peripheral blood mononuclear cells (PBMC). The present study shows significant immunomodulatory effects of these BC preparations in human PBMC, either by enhancing or suppressing the occurrence of a Th-1 type immune response. The amount of lactose present in BC seems to diminish the activity of BC in our test system, since BC with higher amounts of lactose attenuated the stimulatory as well as the suppressive activity of BC.

Molecular cloning, promoter analysis and SNP identification of Italian Nicastrese and Saanen lactoferrin gene.

Lactoferrin (Lf) is an iron-binding glycoprotein found in exocrine secretions including milk. High levels of lactoferrin may have a role in the prevention of microbial infection of the mammary gland. In this report we sequenced and characterized goat lactoferrin cDNA and its promoter region in two different breeds of goat. The complete cDNA comprised 2356 nucleotides, including 38 bp at the 5'-UTR and 194 bp at the 3'-UTR. The open reading frame is 2127 bp long and it encodes a mature protein of 689 aminoacids. A total of 19 nucleotide differences, 11 of them being responsible for 8 aminoacid changes, were identified through the comparison with French, Korean and Tibetan goat lactoferrin cDNAs. About 1700 bp of the lactoferrin gene promoter were sequenced. Sequence analysis revealed a non-canonical TATA box, multiple SP1/GC elements, and other putative binding sites for transcription factors, such as NF-kappaB, STAT3 and AP2. Two SNPs were identified, one of which would seem to create a new putative AP2 consensus sequence. The presence of an additional AP2 binding site could be associated with quantitative differences of such protein fraction, which could enhance all the activities related to such protein, and improve mammary gland defence against bacterial infections.

Lactoferrin enhances efficacy of the BCG vaccine: comparison between two inbred mice strains (C57BL/6 and BALB/c).

The current vaccine for tuberculosis (TB), an attenuated strain of Mycobacterium bovis Bacillus Calmette Guerin (BCG), is effective to prevent childhood onset of the disease, but its efficacy is reduced in adults. One strategy to improve the existing vaccine is to develop more effective adjuvants. Lactoferrin, an iron-binding glycoprotein possessing immune modulatory activities, is a promising adjuvant candidate. The studies presented here examine the effect of lactoferrin to enhance efficacy of the BCG vaccine using a vaccination/challenge protocol (8 weeks boost and challenge at 12 weeks post-boost) that focuses on reduction in development of pathological changes to lung tissue. C57BL/6 and BALB/c mice vaccinated with BCG/lactoferrin exhibited protection upon Mycobacterium tuberculosis (MTB) challenge, showing reduced pulmonary disease pathology and decreased organ bacterial load. In addition, BCG/lactoferrin-treated macrophages isolated from BALB/c mice, which express a relative reduced T(H)1 phenotypic response to MTB antigens compared to the C57BL/6 mouse, were able to activate a higher percentage of IFN-gamma-producing CD4+ splenocytes. Overall, lactoferrin stands as an adjuvant capable of enhancing efficacy of the BCG vaccine through induction of T(H)1 immune responses, even in hosts typically demonstrative of reduced T(H)1 responsiveness to BCG antigens.

Supplementing suckling rats with whey protein concentrate modulates the immune response and ameliorates rat rotavirus-induced diarrhea.

Group A rotaviruses (RV) are the most common causative agents of acute gastroenteritis in children <2 y. The present study was designed to establish the effect of a bovine whey protein concentrate (WPC) in a RV infection model in suckling rats. From d 3 of life, suckling Lewis rats received daily supplements of WPC, WPC plus lactoferrin (LF), standard infant formula (SIF), or water (RV-infected group and an untreated, uninfected reference group). On d 8 of life, heterologous simian RV SA-11 was inoculated orally in the WPC-RV, WPC+LF-RV, SIF-RV, and RV groups. WPC and WPC+LF reduced diarrhea incidence from approximately 90% in RV group to approximately 60% in WPC-RV and WPC+LF-RV groups (P < 0.05), whereas the area under the curve (AUC) of severity along time diminished from approximately 10 AUC in the RV group to approximately 6 AUC in both supplemented groups (P < 0.05). Serum levels of anti-RV antibodies, splenocyte proliferation, and interferon-gamma secretion after specific stimulation were significantly lower in the WPC-RV and WPC+LF-RV groups than in the SIF-RV and RV groups. In the intraepithelial intestinal compartment, RV infection increased the proportion of typical mucosal T cells (IE-T CD8alphaalpha+); however, this modification was controlled by WPC and WPC+LF supplementation. In general, for most of the parameters studied, the SIF-RV and RV groups did not differ. In summary, daily supplementation with WPC or WPC+LF in early life considerably reduces the severity of RV-induced acute gastroenteritis and modulates the immune response against the pathogen.

'Iron-saturated' lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy.

Bovine lactoferrin (bLf), an iron-containing natural defence protein found in bodily secretions, has been reported to inhibit carcinogenesis and the growth of tumours. Here, we investigated whether natural bLf and iron-saturated forms of bLf differ in their ability to augment cancer chemotherapy. bLf was supplemented into the diet of C57BL/6 mice that were subsequently challenged subcutaneously with tumour cells, and treated by chemotherapy. Chemotherapy eradicated large (0.6 cm diameter) EL-4 lymphomas in mice that had been fed iron-saturated bLf (here designated Lf(+)) for 6 weeks prior to chemotherapy, but surprisingly not in mice that were fed lesser iron-saturated forms of bLf, including apo-bLf (4% iron saturated), natural bLf (approximately 15% iron saturated) and 50% iron-saturated bLf. Lf(+)-fed mice bearing either EL-4, Lewis lung carcinoma or B16 melanoma tumours completely rejected their tumours within 3 weeks following a single injection of either paclitaxel, doxorubicin, epirubicin or fluorouracil, whereas mice fed the control diet were resistant to chemotherapy. Lf(+) had to be fed to mice for more than 2 weeks prior to chemotherapy to be wholly effective in eradicating tumours from all mice, suggesting that it acts as a competence factor. It significantly reduced tumour vascularity and blood flow, and increased antitumour cytotoxicity, tumour apoptosis and the infiltration of tumours by leukocytes. Lf(+) bound to the intestinal epithelium and was preferentially taken up within Peyer's patches. It increased the production of Th1 and Th2 cytokines within the intestine and tumour, including TNF, IFN-gamma, as well as nitric oxide that have been reported to sensitize tumours to chemotherapy. Importantly, it restored both red and white peripheral blood cell numbers depleted by chemotherapy, potentially fortifying the mice against cancer. In summary, bLf is a potent natural adjuvant and fortifying agent for augmenting cancer chemotherapy, but needs to be saturated with iron to be effective.

Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world's population. The established vaccine for TB, an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed since 1921. Lactoferrin, an iron-binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine, specifically because of previous reports of lactoferrin enhancement of IL-12 production from macrophages infected with BCG. Different vaccination protocols were investigated for generation of host protective responses against MTB infection using lactoferrin admixed to the BCG vaccine. Resulting effects demonstrate that BCG/lactoferrin increased host protection against MTB infection by decreasing organ bacterial load and reducing lung histopathology; significant reduction in tissue CFUs and pathology were observed post-challenge compared to those seen with BCG alone. Addition of lactoferrin to the vaccine led to reduced pathological damage upon subsequent infection with virulent MTB, with positive results demonstrated when admixed in oil-based vehicle (incomplete Freund's adjuvant, IFA) or when given with BCG in saline. The observed post-challenge results paralleled increasing production of IFN-gamma and IL-6, but only limited changes to proinflammatory mediators TNF-alpha or IL-1beta from BCG-stimulated splenocytes. Overall, these studies indicate that lactoferrin is a useful and effective adjuvant to improve efficacy of the BCG vaccine, with potential to reduce related tissue damage and pulmonary histopathology.

Effect of lactoferrin on selected immune system parameters and the gastrointestinal morphology in growing calves.

Lactoferrin (LF) is a cationic iron-binding glycoprotein that is abundantly expressed and secreted from glandular epithelial cells and a prominent component of the secondary granules of polymorphonuclear neutrophils. Various in vitro and in vivo experiments demonstrate anti-microbial, -viral, -mycotic and -inflammatory effects of LF, associated with modulations of the immune system. Effects of oral administered LF on selected immune system parameters were studied in calves. Five calves were fed LF beginning on day 3 of life with colostral milk and starting on day 6 of life milk replacer enriched with 0.16% LF was fed. The average daily intake of LF per calf was 1.5-1.6 g/day. Additional five calves served as control group with identical treatment except for the LF supplementation. At the end of the study (day 61 of life), all calves were slaughtered and various tissues were sampled for histological and gene-expression studies. LF given orally was shown to act as an immunomodulatory agent by enhancing the size of Peyer's patches in the ileum and increasing blood serum immunoglobulin G levels. In addition, the number of peripheral blood leucocytes increased and mRNA levels of various interleukins (IL) such as IL-1beta, IL-8, IL-10 and interferon gamma (IFNgamma) in those cells in response to LF treatment were enhanced. In blood, the mRNA expression of the pro-inflammatory marker genes IL-1beta and IFNgamma decreased over 10-week treatment. Additionally, LF feeding decreased villus sizes in the jejunum. Together these findings emphasize the ability of LF to stimulate prominent immune system parameters and that it has the capacity to modulate the immune responses in a positive way.

Effects of lactoferrin feeding on growth, feed intake and health of calves.

Lactoferrin (LF) exhibits a broad spectrum of anti-microbial properties and may have regulatory functions in the immune system. In the present study, 40 calves (20 males, 20 females) were used to examine the effects of supplemental bovine LF added to colostrum and milk replacer (at 0.16%) on health, weight development and feed intake during a 70-day experimental period. The calves were allocated to a treatment group (n = 20) and a control group (n = 20); the groups were balanced in terms of sex, live weight and date of birth. Body weight and feed intake were measured at regular intervals. Blood and colostrum samples were collected to determine the content of IgG. In addition, colostrum and milk replacer samples were analysed for their LF concentrations. Significantly higher IgG values were observed in the LF treated than in the control group during the entire feeding experiment from week 2 to week 6. Calves receiving LF had less days of disease with less serious cases of diarrhoea than the control group. Body weight and feed intake were not significantly different between the treatments; in male calves LF-treated animals tended towards higher weight gains. This study indicates that LF is advantageous for health and may therefore be a beneficial supplement in the diets for neonatal calves.