lactoferrin and Bacterial-Infections

The emergence of multidrug-resistant bacterial strains with respect to commercially available antimicrobial drugs has marked a watershed in treatment therapies to fight pathogens and has stimulated research on alternative remedies. Proteins of the innate immune system of mammals have been highlighted as potentially yielding possible treatment options for infections. Lactoferrin (Lf) is one of these proteins; interestingly, no resistance to it has been found. Lf is a conserved cationic nonheme glycoprotein that is abundant in milk and is also present in low quantities in mucosal secretions. Moreover, Lf is produced and secreted by the secondary granules of neutrophils at infection sites. Lf is a molecule of approximately 80 kDa that displays multiple functions, such as antimicrobial, anti-viral, anti-inflammatory, and anticancer actions. Lf can synergize with antibiotics, increasing its potency against bacteria. Lactoferricins (Lfcins) are peptides resulting from the N-terminal end of Lf by proteolytic cleavage with pepsin. They exhibit several anti-bacterial effects similar to those of the parental glycoprotein. Synthetic analog peptides exhibiting potent antimicrobial properties have been designed. The aim of this review is to update understanding of the structure and effects of Lf and Lfcins as anti-bacterial compounds, focusing on the mechanisms of action in bacteria and the use of Lf in treatment of infections in patients, including those studies where no significant differences were found. Lf could be an excellent option for prevention and treatment of bacterial diseases, mainly in combined therapies with antibiotics or other antimicrobials.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Bacterial Infections; Humans; Lactoferrin; Mammals; Peptides

Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.. To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates. Secondarily, we assessed the effects of lactoferrin supplementation to enteral feeds on the duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later.. We used the standard search strategy of Cochrane Neonatal to update our search. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 9), MEDLINE via PubMed (1966 to 20 January 2020), PREMEDLINE (1996 to 20 January 2020), Embase (1980 to 20 January 2020), and CINAHL (1982 to 20 January 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.. In our search, we included randomized controlled trials (RCTs) evaluating enteral lactoferrin supplementation at any dose or duration to prevent sepsis or NEC in preterm neonates.. We used the standard methods of Cochrane Neonatal and the GRADE approach to assess the certainty of evidence.. Meta-analysis of data from twelve randomized controlled trials showed that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical RR 0.82, 95% CI 0.74 to 0.91; typical RD -0.04, 95% CI, -0.06, -0.02; NNTB 25, 95% CI 17 to 50; 12 studies, 5425 participants, low-certainty evidence) and decreased length of hospital stay (MD -2.38, 95% CI, -4.67, -0.09; 3 studies, 1079 participants, low-certainty evidence). Sensitivity analysis including only good methodological certainty studies suggested a decrease in late-onset sepsis with enteral lactoferrin supplementation (typical RR 0.87, 95% CI, 0.78, 0.97; typical RD -0.03, 95% CI, -0.05, -0.0; 9 studies, 4702 participants, low-certainty evidence). There were no differences in NEC stage II or III (typical RR 1.10, 95% CI, 0.86, 1.41; typical RD -0.00, 95% CI, -0.02, 0.01; 7 studies, 4874 participants; low-certainty evidence) or 'all-cause mortality' (typical RR 0.90, 95% CI 0.69, 1.17; typical RD -0.00, 95% CI, -0.01, 0.01; 11 studies, 5510 participants; moderate-certainty evidence). One study reported no differences in neurodevelopmental testing by Mullen's or Bayley III at 24 months of age after enteral lactoferrin supplementation (one study, 292 participants, low-certainty evidence). Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.25, 95% CI 0.14 to 0.46; RD -0.13, 95% CI -0.18 to -0.08; NNTB 8, 95% CI 6 to 13; 3 studies, 564 participants; low-certainty evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; 1 study, 496 participants; very low-certainty evidence), but not 'all-cause mortality' (very low-certainty evidence). Lactoferrin supplementation to enteral feeds with or without probiotics had no effect on CLD, duration of mechanical ventilation or threshold retinopathy of prematurity (low-certainty evidence). Investigators reported no adverse effects in the included studies.. We found low-certainty evidence from studies of good methodological quality that lactoferrin supplementation of enteral feeds decreases late-onset sepsis but not NEC ≥ stage II or 'all cause mortality' or neurodevelopmental outcomes at 24 months of age in preterm infants without adverse effects. Low- to very low-certainty evidence suggests that lactoferrin supplementation of enteral feeds in combination with probiotics decreases late-onset sepsis and NEC ≥ stage II in preterm infants without adverse effects, however, there were few included studies of poor methodological quality. The presence of publication bias and small studies of poor methodology that may inflate the effect size make recommendations for clinical practice difficult.

Topics: Administration, Oral; Bacterial Infections; Cause of Death; Chronic Disease; Enteral Nutrition; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lacticaseibacillus rhamnosus; Lactoferrin; Lung Diseases; Mycoses; Numbers Needed To Treat; Probiotics; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Sepsis

Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.. Primary objective 1. To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates Secondary objectives 1. To determine the effects of lactoferrin supplementation to enteral feeds to prevent neonatal sepsis and/or NEC on duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later2. To determine the adverse effects of lactoferrin supplementation for prophylaxis of neonatal sepsis and/or NECWhen data were available, we analyzed the following subgroups.1. Gestational age < 32 weeks and 32 to 36 weeks2. Birth weight < 1000 g (extremely low birth weight (ELBW) infants) and birth weight < 1500 g (very low birth weight (VLBW) infants)3. Type of feeding: breast milk versus formula milk SEARCH METHODS: We used the search strategy of the Cochrane Neonatal Review Group (CNRG) to update our search in December 2016. We searched the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PREMEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as trial registries and conference proceedings.. Randomized controlled trials (RCTs) evaluating oral lactoferrin at any dose or duration to prevent sepsis or NEC in preterm neonates.. Review authors used standard methods of the CNRG.. This review includes six RCTs. Trial results show that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical risk ratio (RR) 0.59, 95% confidence interval (CI) 0.40 to 0.87; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 17, 95% CI 10 to 50; six trials, 886 participants; low-quality evidence) and NEC stage II or III (typical RR 0.40, 95% CI 0.18 to 0.86; typical RD -0.04, 95% CI -0.06 to -0.01; NNTB 25, 95% CI 17 to 100; four studies, 750 participants; low-quality evidence). Lactoferrin supplementation did not have an effect on "all-cause mortality" (typical RR 0.65, 95% CI 0.37 to 1.11; typical RD -0.02, 95% CI -0.05 to 0; six studies, 1041 participants; low-quality evidence).Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.27, 95% CI 0.12 to 0.60; RD -0.13, 95% CI -0.19 to -0.06; NNTB 8, 95% CI 5 to 17; one study, 321 participants; low-quality evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; one study, 496 participants; low-quality evidence), but not "all-cause mortality" (low-quality evidence).Lactoferrin supplementation to enteral feeds with or without probiotics decreased bacterial and fungal sepsis but not CLD or length of hospital stay (low-quality evidence). Investigators reported no adverse effects and did not evaluate long-term neurological outcomes and PVL.. Evidence of low quality suggests that lactoferrin supplementation to enteral feeds with or without probiotics decreases late-onset sepsis and NEC stage II or III in preterm infants without adverse effects. Completed ongoing trials will provide data from more than 6000 preterm neonates, which may enhance the quality of the evidence. Clarification regarding optimal dosing regimens, types of lactoferrin (human or bovine), and long-term outcomes is needed.

Topics: Administration, Oral; Bacterial Infections; Cause of Death; Chronic Disease; Enteral Nutrition; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lacticaseibacillus rhamnosus; Lactoferrin; Lung Diseases; Mycoses; Numbers Needed To Treat; Probiotics; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Sepsis

Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal, and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation, and early initiation of therapy are required to prevent adverse outcomes. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis.

Topics: Adaptive Immunity; Anti-Infective Agents; Antibodies, Monoclonal; Antifungal Agents; Bacterial Infections; Biomarkers; Blood Cell Count; C-Reactive Protein; Candidiasis; Escherichia coli Infections; Fluconazole; Genomics; Humans; Immunity, Innate; Immunoglobulins, Intravenous; Infant, Newborn; Infant, Newborn, Diseases; Lactoferrin; Polymerase Chain Reaction; Predictive Value of Tests; Proteomics; Risk Factors; Sepsis; Streptococcal Infections; Streptococcus agalactiae

Acute and chronic inflammation commonly occurs throughout the oral cavity. The most common causes are physical damage and microbial infections, and less frequently immune reactions and malignant changes. All of these processes result in the induction of antimicrobial peptides, chemokines and cytokines that lead to cellular infiltrates, a vascular response, tissue destruction and cellular proliferation. A fascinating concept developing in the current literature suggests that antimicrobial peptides modulate the production of chemokines, cytokines and other cellular mediators and that this may have a larger ramification as an underlying mechanism mediating inflammation. Here, we propose that the ability of antimicrobial peptides to induce chemokines and anti-inflammatory or proinflammatory cytokines plays an important role in the early events of oral inflammation and may be a target for the prevention or treatment of oral inflammatory conditions.

Topics: Anti-Inflammatory Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Cytokines; Humans; Immunity, Innate; Immunomodulation; Inflammation; Lactoferrin; Lipopolysaccharides; Mouth; Protein Binding; Saliva

Iron homeostasis in the mammalian host limits the availability of iron to invading pathogens and is thought to restrict iron availability for microbes inhabiting mucosal surfaces. The presence of surface receptors for the host iron-binding glycoproteins transferrin (Tf) and lactoferrin (Lf) in globally important Gram-negative bacterial pathogens of humans and food production animals suggests that Tf and Lf are important sources of iron in the upper respiratory or genitourinary tracts, where they exclusively reside. Lf receptors have the additional function of protecting against host cationic antimicrobial peptides, suggesting that the bacteria expressing these receptors reside in a niche where exposure is likely. In this review we compare Tf and Lf receptors with respect to their structural and functional features, their role in colonization and infection, and their distribution among pathogenic and commensal bacteria.

Topics: Animals; Bacteria; Bacterial Infections; Bacterial Proteins; Host-Pathogen Interactions; Humans; Iron; Lactoferrin; Transferrin

Newborns are at increased risk of infection due to genetic, epigenetic, and environmental factors. Herein we examine the roles of the neonatal innate immune system in host defense against bacterial and viral infections. Full-term newborns express a distinct innate immune system biased toward T(H)2-/T(H)17-polarizing and anti-inflammatory cytokine production with relative impairment in T(H)1-polarizing cytokine production that leaves them particularly vulnerable to infection with intracellular pathogens. In addition to these distinct features, preterm newborns also have fragile skin, impaired T(H)17-polarizing cytokine production, and deficient expression of complement and of antimicrobial proteins and peptides (APPs) that likely contribute to susceptibility to pyogenic bacteria. Ongoing research is identifying APPs, including bacterial/permeability-increasing protein and lactoferrin, as well as pattern recognition receptor agonists that may serve to enhance protective newborn and infant immune responses as stand-alone immune response modifiers or vaccine adjuvants.

Topics: Antimicrobial Cationic Peptides; Bacterial Infections; Blood Proteins; Cytokines; Humans; Immunity, Innate; Infant, Newborn; Inflammasomes; Lactoferrin; Lectins, C-Type; Receptors, Cytoplasmic and Nuclear; Sepsis; Signal Transduction; Toll-Like Receptors; Virus Diseases

There is an urgent need to develop new antimicrobial drugs especially for combating the rise of infections caused by multi-resistant pathogens such as MRSA and VRSA. The problem of antibiotic resistant micro-organisms is expected to increase disproportionally and controlling of infections is becoming difficult because of the rapid spread of those micro-organisms. Primary therapy with classical antibiotics is becoming more ineffective. Combinational therapy of antibiotics with antimicrobial peptides (AMP's) has been suggested as an alternative approach to improve treatment outcome. Their unique mechanism of action and safety profile makes AMP's appealing candidates for simultaneous or sequential use in different cases of infections. In this review, for antimicrobial treatment the application of synthetic antimicrobial peptide hLF(1-11), derived from the first 11 amino acids of human lactoferrin is evaluated in both pre-clinical and clinical settings. Present information indicates that this derivate from lactoferrin is well tolerated in pre-clinical tests and clinical trials and thus hLF(1-11) is an interesting candidate for further exploration in various clinical indications of obscure infections, including meningitis. Another approach of using AMP's is their use in prevention of infections e.g. as coating for dental or bone implants or in biosensing applications or useful as infection specific radiopharmaceutical.

Topics: Amino Acid Sequence; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Candida; Chemistry Techniques, Synthetic; Clinical Trials as Topic; Drug Discovery; Drug Evaluation; Drug Resistance, Microbial; Drug Synergism; Humans; Lactoferrin; Methicillin-Resistant Staphylococcus aureus; Mice; Molecular Sequence Data; Mycoses; Peptide Fragments

Sepsis-related morbidity and mortality is an increasing concern in all neonatal intensive care units, with reported incidences that are dramatically high regardless of the improvements in the quality of neonatal assistance. Antimicrobial resistance is also becoming a global and regional threat to public health. Neonatal sepsis include bloodstream, urine, cerebrospinal, peritoneal infections, and are classified as early-onset (occurring <3 days of life, EOS) and late-onset sepsis (LOS), i.e., infections arising after the perinatal period. Whereas prevention of EOS relies mainly on maternal-perinatal policies, attempts to reduce LOS incidence are a task merely for neonatologists but are hampered by non-specific clinical features, inadequate sensitivity of diagnostic tests, and late recognition. The frequent occurrence of late neurodevelopmental impairment after LOS challenges neonatologists to seek effective preventative strategies rather than more efficacious antibiotics for treatment. In the area of prevention, consistent evidence is accumulating on fluconazole--for prevention of fungal LOS--and, more recently, on bovine lactoferrin for prevention of both bacterial and fungal LOS: this innate immune system glycoprotein plays an important role in "in vivo" host defenses, and has been shown effective in a multicenter RCT recently published on VLBW neonates. Future studies are warranted to better elucidate the extent of the prevention provided by Ictoferrin and to identify the most suitable dosages to be administered.

Topics: Age of Onset; Animals; Bacterial Infections; Bacterial Translocation; Cattle; Fluconazole; Humans; Incidence; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lactoferrin; Mice; Mycoses; Probiotics; Randomized Controlled Trials as Topic; Risk Factors; Sepsis

A considerable array of diseases are now recognized to be associated with misplacement of iron. Excessive deposits of the metal in sensitive tissue sites can result in formation of destructive hydroxyl radicals as well as in stimulation of growth of neoplastic and microbial cell invaders. To counteract potential iron damage, hosts employ the iron chelators, transferrin and lactoferrin. These proteins have been recently developed into pharmaceutical products. Additionally, a variety of low molecular mass iron chelators are being used/tested to treat whole body iron loading, and specific diseases for which the metal is a known or suspected risk factor.

Topics: Animals; Bacterial Infections; Deferoxamine; Free Radicals; Humans; Iron; Iron Chelating Agents; Iron Overload; Lactoferrin; Mycoses; Neoplasms; Transferrin

The first function attributed to lactoferrin (Lf), an iron binding protein belonging to the non-immune natural defences, was antimicrobial activity that depended on its capacity to sequester iron. Iron-independent microbicidal activities, requiring direct interaction between this cationic protein and microbial surface components, were later demonstrated. Many other anti-microbial and anti-viral functions have since been ascribed to Lf. In mucosal secretions, iron and Lf modulate the motility and aggregation of pathogenic bacteria. Lf inhibits bacterial adhesion on abiotic surfaces through ionic binding to biomaterials, or specific binding to bacterial structures or both. Lf inhibition of bacterial adhesion to host cells requires Lf binding to bacteria and/or host cells. Lf hinders microbial internalization by binding to both glycosaminoglycans and bacterial proteins which can be degraded by Lf-mediated proteolysis. Moreover, Lf internalisation and localisation to the host cell nuclei could modulate bacterial entry into cells through gene regulation. Finally, the capability of Lf to exert antiviral activity, through its binding to host cells and/or viral particles, strengthens the idea that it is an important brick in the mucosal wall, effective against both microbial and viral attacks.

Topics: Animals; Anti-Infective Agents; Antiviral Agents; Bacterial Infections; Humans; Lactoferrin; Virus Diseases

Topics: Adult; Age Factors; Aged; Antimicrobial Cationic Peptides; Bacterial Infections; Female; Humans; Immunoglobulins; Lactoferrin; Male; Middle Aged; Muramidase; Phospholipases A; Sensitivity and Specificity; Tears

New cysteine protease inhibitors in human tears and milk and their medical significance are reviewed in this paper. As protective components against bacterial infection in the eyes, we detected four kinds of anti-bacterial proteins in normal human tears including lysozyme and three kinds of cysteine protease inhibitors. Using our reverse zymography of normal tears, three kinds of cysteine protease inhibitors were found to be 78kDa, 20kDa and 15kDa and were determined to be lactoferrin, Von Ebner's Gland (VEG) protein and cystatin S, respectively. All of them belong to the cystatin super family and VEG protein and cystatin S are well known cysteine protease inhibitors. The C-terminus area 17mer peptide, Y679-K695, of lactoferrin showed strong homology with a common active domain of the cystatin family and the synthesized peptide showed inhibition of cysteine proteases. Not only were disease-specific changes found in these inhibitor profiles, but also disease-specific new inhibitors in patients tears with certain autoimmune diseases. A 35kDa inhibitor, which was detected specifically in tears with Behcet's disease, an typical autoimmune disease, was determined to be a lacrimal acidic proline-rich protein based on the N-terminus sequence analysis. A 65kDa inhibitor of tears with Harada's autoimmune disease was determined to be an Ig heavy chain V-III region. In addition, lactoferrin content in Harada's disease was very low. We found two cathepsin inhibitors in bovine milk using reverse zymography, namely lactoferrin and beta-casein. The L133-Q151, in the human beta-casein molecule is the active inhibitory domain. They may play an important role in antiseptic and anti-infectious functions.

Topics: Animals; Autoimmune Diseases; Bacteria; Bacterial Infections; Caseins; Cattle; Clinical Enzyme Tests; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Humans; Lactoferrin; Milk; Molecular Weight; Tears

The continuing unresolved debate over the interaction of iron and infection indicates a need for quantitative review of clinical morbidity outcomes. Iron deficiency is associated with reversible abnormalities of immune function, but it is difficult to demonstrate the severity and relevance of these in observational studies. Iron treatment has been associated with acute exacerbations of infection, in particular, malaria. Oral iron has been associated with increased rates of clinical malaria (5 of 9 studies) and increased morbidity from other infectious disease (4 of 8 studies). In most instances, therapeutic doses of oral iron were used. No studies in malarial regions showed benefits. Knowledge of local prevalence of causes of anemia including iron deficiency, seasonal malarial endemicity, protective hemoglobinopathies and age-specific immunity is essential in planning interventions. A balance must be struck in dose of oral iron and the timing of intervention with respect to age and malaria transmission. Antimalarial intervention is important. No studies of oral iron supplementation clearly show deleterious effects in nonmalarious areas. Milk fortification reduced morbidity due to respiratory disease in two very early studies in nonmalarious regions, but this was not confirmed in three later fortification studies, and better morbidity rates could be achieved by breast-feeding alone. One study in a nonmalarious area of Indonesia showed reduced infectious outcome after oral iron supplementation of anemic schoolchildren. No systematic studies report oral iron supplementation and infectious morbidity in breast-fed infants in nonmalarious regions.

Topics: Administration, Oral; Animals; Antibody Formation; Bacterial Infections; Breast Feeding; Confidence Intervals; Confounding Factors, Epidemiologic; Controlled Clinical Trials as Topic; Disease Susceptibility; Endemic Diseases; Female; Humans; Immunity, Cellular; Immunocompromised Host; Incidence; Infant; Infections; Iron; Iron Deficiencies; Lactoferrin; Malaria; Milk; Models, Animal; Odds Ratio; Parasitic Diseases; Pneumonia; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Time Factors; Transferrin

Topics: Amino Acid Sequence; Animals; Bacteria; Bacterial Infections; Fungi; Humans; Infant; Infant, Newborn; Iron; Lactoferrin; Milk; Milk, Human; Viruses

The in vivo evidence of the antimicrobial and antiviral activity of bovine milk and colostrum derived components are reviewed with special emphasis on lactoferrin and lactoperoxidase. Their mode of action and the rationale for their application in efficacy trials with rodents, farm animals, fish and humans, to give protection against infectious agents, are described. A distinction is made between efficacy obtained by oral and non-oral administration of these non-specific defence factors which can be commercially applied in large quantities due to major achievements in dairy technology. From the in vivo studies one can infer that lactoferrin and lactoperoxidase are very promising, naturally occurring antimicrobials for use in fish farming, husbandry, oral hygiene and functional foods. Other promising milk-derived compounds include lipids, from which anti-infective degradation products are generated during digestion, and antimicrobial peptides hidden in the casein molecules.

Topics: Animals; Bacterial Infections; Cattle; Cattle Diseases; Colostrum; Female; Fish Diseases; Humans; Infant, Newborn; Lactoferrin; Lactoperoxidase; Milk; Neutrophils; Oncorhynchus mykiss; Pregnancy; Swine; Swine Diseases; Virus Diseases

Lactoferrin and lysozyme are two important, naturally occurring antibacterial proteins found in saliva, nasal secretions, milk, mucus, serum and in the lysosomes of neutrophils and macrophages. Both proteins bind specifically to glucose-modified proteins bearing advanced glycation endproducts (AGEs). Exposure to AGE-modified proteins blocks the bacterial agglutination and bacterial killing activities of lactoferrin and also inhibits the bactericidal and enzymatic activity of lysozyme. Peptide mapping by AGE ligand blot revealed two AGE-binding domains in lactoferrin, and a single AGE-binding domain in lysozyme. None of these AGE-binding domains displayed any significant homology in their primary sequences; however, a common 17-18 amino acid cysteine loop motif (CX15-16C) was identified among them, which we named an ABCD motif (AGE-Binding Cysteine-bounded Domain). Similar domains are also present in other antimicrobial proteins such as defesins. Hydrophilicity analysis indicated that each of these ABCD loops is markedly hydrophilic. Synthetic peptides, corresponding to these motifs in lactoferrin and lysozyme, exhibited AGE-binding activity. Since diabetes is associated with abnormally high levels of tissue and serum AGEs, the elevated AGEs may inhibit endogenous antibacterial proteins by binding to the conserved ABCD motif, thereby increasing susceptibility to bacterial infections in diabetic individuals. These results may provide a basis for the development of new approaches to prevent diabetic infections.

Topics: Amino Acid Sequence; Bacterial Infections; Diabetes Complications; Diabetes Mellitus; Glycosylation; Humans; Lactoferrin; Ligands; Molecular Sequence Data

Iron is essential to all microorganisms. To obtain iron from the very low concentrations present in their environment, microorganisms have developed sophisticated mechanisms such as the siderophore system. As a primitive defense mechanism, humans have developed mechanisms to withhold iron from microorganisms. Iron-binding proteins such as transferrin, ferritin, and lactoferrin have a central role in human ferrokinetics. These iron-binding proteins also participate in the process of decreasing iron availability for the microorganisms. They do so by decreasing iron reutilization. Anemia of inflammation (previously called anemia of chronic disease) is seen in the setting of infectious, inflammatory, and neoplastic diseases. It results, in part, from changes in the intracellular metabolism of iron. Alterations of iron physiology seen in many clinical circumstances make excess iron available to microorganisms, thus enhancing their pathogenicity. Understanding the molecular basis of iron withholding by the human host, both in the absence of and during infection, and that of iron acquisition by microorganisms may provide us with new and innovative antimicrobial agents and vaccines.

Topics: Anemia; Bacteria; Bacterial Infections; Blood Transfusion; Carrier Proteins; Conalbumin; Deferoxamine; Diabetic Ketoacidosis; Ferritins; Hemochromatosis; Hemolysis; Humans; Inflammation; Iron; Iron-Binding Proteins; Lactoferrin; Transferrin; Transferrin-Binding Proteins

Topics: Bacterial Infections; Carrier Proteins; Female; Humans; Lactoferrin; Transferrin

In the mammary gland of cattle there is a complex defense system of non-specific and specific reactions available preventing the invasion of pathogenic bacteria. Most infections occur via the teat canal, so teat canal keratin (SKK) is of particular importance in non-specific defense of the gland. The SKK serves as a physical barrier, and bacteriostatic and/or bactericidal effects of SKK lipids and proteins against certain mastitis bacteria could be demonstrated. By increasing the concentrations of lactoferrin and lysozyme in milk a reduction of mastitis frequencies could be observed. However, those high concentrations in the proteins occur only during the dry period of the cow. An improvement of the mastitis situation would also appear possible by increasing phagocytosis. The numerous trials intended to reduce mastitis by improving specific protection showed no significant success. Therefore, the most successful and cheapest means to achieve udder health remains the strict and consistent hygiene of housing, animals and mammary glands.

Topics: Animals; Bacterial Infections; Cattle; Female; Keratins; Lactoferrin; Lipids; Mammary Glands, Animal; Mastitis, Bovine; Milk; Milk Proteins; Muramidase; Phagocytosis

The role of iron in certain clinical infections is revealed. In normal persons the antibacterial and antifungal properties of blood and other tissue fluids cannot be maintained unless there are exceptionally low levels of available iron. This is controlled by the presence of the unsaturated iron-binding proteins, transferrin and lactoferrin. In several clinical conditions an abnormal availability of iron is responsible for fatal septicaemia. This is because the phagocytic system is overwhelmed by rapidly growing organisms when iron is freely available.

Topics: Bacterial Infections; Candidiasis; Carrier Proteins; Disease Susceptibility; Humans; Iron; Iron-Binding Proteins; Lactoferrin; Leukemia; Transferrin; Transferrin-Binding Proteins; Virulence

Topics: Bacterial Infections; Female; Humans; Immunity, Innate; Lactoferrin; Pregnancy; Pregnancy Complications, Infectious; Puerperal Infection

Topics: Animals; Bacterial Infections; DNA, Bacterial; Ferritins; Haptoglobins; Heme; Hemin; Hemoglobins; Humans; Iron; Iron Chelating Agents; Lactoferrin; RNA, Bacterial; Transferrin

Extracellular killing provides an attractive hypothesis to explain the rapid alveolar killing of inhaled bacterial pathogens in the absence of conventional opsonins for phagocytosis. Some evidence of extracellular killing of inhaled pneumococci has been obtained using histologic studies and bronchoalveolar lavage. Although studies of the antimicrobial activity of lung lavage fluid in vitro have given variable results, a variety of antimicrobial factors have been detected in lung lavage fluids. Studies of lysozyme, peptides, iron binding proteins, free fatty acids and other factors that are found free in lung lavage fluid indicate that some of these factors could be a part of extracellular pulmonary host defenses. However, their precise role is not known. A survey of mechanisms of extracellular killing shows that granulocytes, monocytes, macrophages, and T lymphocytes all have the capacity to kill extracellularly in vitro in some circumstances. It remains to be determined which of these diverse mechanisms operate within the lung and how they function in relationship to other host defenses.

Topics: Animals; Bacterial Infections; Bronchoalveolar Lavage Fluid; Fatty Acids, Nonesterified; Humans; Lactoferrin; Leukocytes; Lung; Muramidase; Pancreatic Elastase; Peptides; Phagocytosis; Pulmonary Alveoli; Pulmonary Surfactants; Transferrin

Bacterial infection may be responsible for mild self-limiting disease, chronic disease or acute and devasting ocular destruction. This paper and those that follow deal with some of the clinical forms of disease which are encountered, the bacteria responsible, the mechanism of invasion and the natural defences and clinical management, including selection and delivery of antibiotics.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Bacteriolysis; Blood Proteins; Ceruloplasmin; Complement Activation; Eye Diseases; Humans; Immunoglobulin A; Lactoferrin; Muramidase; Proteins; Tears

Topics: Anemia, Hypochromic; Animals; Bacteria; Bacterial Infections; Bacterial Outer Membrane Proteins; Binding, Competitive; Biological Transport; Disease Susceptibility; Hemin; Humans; Hydroxamic Acids; Hydroxybenzoates; Iron; Lactoferrin; Macromolecular Substances; Protein Binding; Receptors, Cell Surface; Species Specificity; Transferrin; Virulence

Topics: Administration, Oral; Animals; Bacterial Infections; Bacterial Vaccines; Gastric Acid; Humans; Immunity, Cellular; Immunity, Innate; Immunization, Passive; Immunoglobulin A; Interferons; Intestinal Diseases; Intestinal Diseases, Parasitic; Intestinal Mucosa; Intestines; Lactoferrin; Muramidase; Vaccination; Vaccines; Vaccines, Attenuated

Topics: Bacterial Infections; Bacterial Physiological Phenomena; Blood Proteins; Granulocytes; Humans; Hydrolases; Lactoferrin; Lysosomes; Mycoses; Neutrophils; Oxygen; Oxygen Consumption; Phagocytosis

The transferrins are iron-binding proteins with molecular weights of around 80,000, which interact with a maximum of two ferric atoms per each protein molecule. The best known transferrins are the serotransferrins from animal sera, lactoferrins from milk, and conalbumin from egg-white. The iron-deficient transferrins will inhibit the growth of certain bacteria and fungi by making iron unavailable for bacterial metabolism. Such activity is abolished if the transferrin is saturated with iron. Many organisms can produce small molecular-weight iron-binding compounds called siderophores that can successfully utilize the iron sequestered by the transferrins. Such organisms are very virulent. Overwhelming evidence is now available to indicate that the transferrins play an important role in mammalian host-defense mechanisms. Thus, iron injections into animals infected with virulent bacteria result in increased death rates, and parenteral iron administration to human infants predisposes them to fatal septicemia. On the other hand, in cases of systemic infection, the organism responds by lowering its total serum iron, so as to make the serotransferrin present less saturated with iron. This phenomenon is called nutritional immunity. The iron apparently moves into the storage tissues from the circulation, and furthermore, it is withheld from circulation by the reticuloendothelial system. Laboratory results in such cases indicate low total serum iron levels and high unsaturated iron-binding activity values, thus increasing the bacteriostatic effects of the serotransferrins. Increased lactoferrin levels are observed in the milks of mastitic cattle.

Topics: Anemia, Hypochromic; Animals; Bacteria; Bacterial Infections; Carrier Proteins; Conalbumin; Female; Fungi; Humans; Hydroxamic Acids; Immunity, Innate; Iron; Iron Chelating Agents; Iron-Binding Proteins; Lactoferrin; Leukemia; Milk, Human; Mycoses; Pregnancy; Siderophores; Transferrin; Transferrin-Binding Proteins

Topics: Animals; Bacterial Infections; Gallium Radioisotopes; Humans; Infections; Lactoferrin; Leukocytes; Neoplasms; Radionuclide Imaging

Topics: Bacterial Infections; Digestive System; Gastrointestinal Diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Absorption; Iron; Lactoferrin; Lactoglobulins; Milk, Human

Topics: Animals; Antibodies, Viral; Bacterial Infections; Female; Hot Temperature; Humans; Immunoglobulin A, Secretory; Interferons; Intestines; Lactoferrin; Lactoperoxidase; Leukocytes; Lipids; Milk, Human; Transferrin; Virus Diseases

Topics: Animals; Bacteria; Bacterial Infections; Carrier Proteins; Colostrum; Humans; Iron; Lactoferrin; Mice; Milk, Human; Neutrophils; Phagocytosis; Protein Binding; Species Specificity; Transferrin

Iron, as participant of many biological processes is a prerequisite for life. Uptake, internal transport and storage by organisms is handled by highly specialized chemical systems endowed with strong metal binding affinities. Apart from the homeostatic function of iron-binding compounds they appear of significance for inter-species interactions. Thus, by tight binding transferrin withholds the iron from invading microorganisms required for their optimal growth. This bacteriostatic property of the iron transport protein is however partially overcome by small molecular substances synthesized by bacteria and successfully competing for the metal. The balance of such interaction is a complex one. Yet, strong evidence points to the crucial importance of the amount of iron offered by a host to infecting agents for determining the fate of bacterial disease.

Topics: Anemia, Hypochromic; Animals; Bacteria; Bacterial Infections; Biological Transport; Guinea Pigs; Humans; Iron; Lactoferrin; Mice; Rats; Siderosis; Transferrin

Lactoferrin and lactoperoxidase have antimicrobial effects against oral pathogens. This randomized, double-blinded, placebo-controlled parallel group study tested the efficacy of a lactoferrin and lactoperoxidase-containing tablet (LF + LPO tablet) in improving the oral hygiene status of older individuals.. A total of 46 participants (31 nursing home residents and 15 healthy older individuals) were randomly assigned to receive either lactoferrin and lactoperoxidase-containing tablets or placebo tablets, and were asked to suck on a tablet after every meal for 8 weeks. Oral and bacteriological assessments were carried out at baseline, 4 weeks and 8 weeks.. A total of 47 participants (test group n = 20; mean age 80.4 ± 6.4 years; placebo group n = 17; mean age 85.9 ± 6.7 years) were included in the efficacy analysis. In the test group, the total number of bacteria in the tongue coating was significantly reduced at 4 and 8 weeks compared with that at baseline, and the number of Porphyromonas gingivalis and Fusobacterium nucleatum was significantly reduced at 8 weeks. The total number of bacteria and the number of P. gingivalis in the supragingival plaque were significantly reduced at 8 weeks. Furthermore, there was a significant difference in the change in the number of P. gingivalis in supragingival plaque at 8 weeks between the two groups.. Lactoferrin and lactoperoxidase-containing tablet ingestion showed antibacterial effects on periodontal bacteria present in the tongue coating and supragingival plaque, indicating that long-term ingestion could improve the oral hygiene of older individuals. Geriatr Gerontol Int 2017; 17: 714-721.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Bacterial Infections; Colony Count, Microbial; Double-Blind Method; Female; Follow-Up Studies; Food; Food Analysis; Gingivitis; Humans; Lactoferrin; Lactoperoxidase; Male; Mouth Mucosa; Oral Hygiene; Retrospective Studies; Saliva

Topics: Antibody Affinity; Bacterial Infections; Disease Susceptibility; Double-Blind Method; Energy Intake; Escherichia coli; Female; Food, Fortified; Guatemala; Humans; Immunoglobulin A, Secretory; Lactoferrin; Milk, Human; Nutrition Disorders; O Antigens; Pregnancy; Tetanus Toxoid

This study aimed to evaluate the diagnostic efficacies of selected inflammatory and intestinal biomarkers in cases of infectious and non-infectious diarrhoea in dogs.. A total of 60 dogs, 12 healthy (Control Group) and 48 with diarrhoea were used. Viral, Bacterial, Parasitic (infectious) and Nutritional diarrhoea (non-infectious) subgroups (n: 12) were formed according to the aetiology, on the basis of clinical and laboratory examinations. Selected inflammatory and intestinal biomarkers (Calgranulin, S100A12; Lactoferrin, LCTF; C-reactive protein, CRP) were measured both in serum and faecal samples.. Compared to the Control and Nutritional Diarrhoea groups, the infectious diarrhoea groups had higher serum S100A12, LCTF, CRP, blood urea nitrogen, creatinine (CR), alanine transaminase and alkaline phosphatase, and lower glucose (GLU), sodium (Na) and potassium (K) concentrations (p < 0.05); Viral and Parasitic Diarrhoea groups had lower serum albumin (ALB) and total protein (TP) concentrations (p < 0.05). Faecal S100A12, LCTF and CRP concentrations were higher in infectious diarrhoea groups compared to the Control and Nutritional Diarrhoea groups (p < 0.05). Faecal LCTF and CRP concentrations were higher in the Bacterial Diarrhoea group than in the Viral and Parasitic Diarrhoea groups (p < 0.05).. It was determined that serum (area under curve, AUC: 0.842 and 0.956) and faecal (AUC: 0.975 and 0.786) S100A12 and CRP concentrations in viral diarrhoea; serum (AUC: 0.956) and faecal (AUC: 0.992) LCTF concentrations in bacterial diarrhoea have diagnostic values in the diagnosis of the presence of intestinal inflammation and damage and can be used in the differential diagnosis of infectious and non-infectious diarrhoea.

Topics: Animals; Bacterial Infections; Biomarkers; Diarrhea; Dog Diseases; Dogs; Lactoferrin; Leukocyte L1 Antigen Complex; S100A12 Protein

Chimeric peptides containing short sequences derived from bovine Lactoferricin (LfcinB) and Buforin II (BFII) were synthetized using solid-phase peptide synthesis (SPPS) and characterized via reversed-phase liquid chromatography and mass spectrometry. The chimeras were obtained with high purity, demonstrating their synthetic viability. The chimeras' antibacterial activity against Gram-positive and Gram-negative strains was evaluated. Our results showed that all the chimeras exhibited greater antibacterial activity against the evaluated strains than the individual sequences, suggesting that chemical binding of short sequences derived from AMPs significantly increased the antibacterial activity. For each strain, the chimera with the best antibacterial activity exerted a bacteriostatic and/or bactericidal effect, which was dependent on the concentration. It was found that: (i) the antibacterial activity of a chimera is mainly influenced by the linked sequences, the palindromic motif RLLRRLLR being the most relevant one; (ii) the inclusion of a spacer between the short sequences did not significantly affect the chimera's synthesis process; however, it enhanced its antibacterial activity against Gram-negative and Gram-positive strains; on the other hand, (iii) the replacement of Arg with Lys in the LfcinB or BFII sequences improved the chimeras' synthesis process without significantly affecting their antibacterial activity. These results illustrate the great importance of the synthesis of chimeric peptides for the generation of promising antibacterial peptides.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cattle; Humans; Lactoferrin; Peptide Fragments; Proteins; Solid-Phase Synthesis Techniques

Antimicrobial peptides are receiving increasing attention as potential therapeutic agents for treating biofilm-related infections of the oral cavity. Many bacteria residing in biofilms exhibit an enhanced antibiotic tolerance, which grants intrinsically susceptible microorganisms to survive lethal concentrations of antibiotics. In this study, we examined the effects of two endogenous human antimicrobial peptides, LL-37 and human Lactoferricin, on the antibiotic drug efficacy of amoxicillin, clindamycin and metronidazole in two types of polymicrobial biofilms, which aimed to represent frequent oral diseases: (1) facultative anaerobic (Streptococcus mutans, Streptococcus sanguinis, Actinomyces naeslundii) and (2) obligate anaerobic biofilms (Veillonella parvula, Parvimonas micra, Fusobacterium nucleatum). LL-37 and Lactoferricin enhanced the anti-biofilm effect of amoxicillin and clindamycin in facultative anaerobic biofilms. Metronidazole alone was ineffective against facultative anaerobic biofilms, but the presence of LL-37 and Lactoferricin led to a greater biofilm reduction. Obligate anaerobic biofilms showed an increased drug tolerance to amoxicillin and clindamycin, presumably due to metabolic downshifts of the bacteria residing within the biofilm. However, when combined with LL-37 or Lactoferricin, the reduction of obligate anaerobic biofilms was markedly enhanced for all antibiotics, even for amoxicillin and clindamycin. Furthermore, our results suggest that antimicrobial peptides enhance the dispersion of matured biofilms, which may be one of their mechanisms for targeting biofilms. In summary, our study proves that antimicrobial peptides can serve as an auxiliary treatment strategy for combatting enhanced antibiotic tolerance in bacterial biofilms.

Topics: Amoxicillin; Anti-Bacterial Agents; Antimicrobial Peptides; Bacteria, Anaerobic; Bacterial Infections; Biofilms; Clindamycin; Humans; Lactoferrin; Metronidazole; Microbial Sensitivity Tests; Mouth Diseases

Lactoferrin (Lf) is a conserved iron-binding glycoprotein with antimicrobial activity, which is present in secretions that recover mucosal sites regarded as portals of invaded pathogens. Although numerous studies have focused on exogenous Lf, little is known about its expression of endogenous Lf upon bacterial infection. In this study, we investigated the distribution of Lf in mice intestine during

Topics: Animals; Bacterial Infections; Disease Models, Animal; Escherichia coli; Inflammation; Intestines; Lactoferrin; Male; Mice, Inbred C57BL; Neutrophils

Lactoferrin is a nutrient classically found in mammalian milk. It binds iron and is transferred via a variety of receptors into and between cells, serum, bile, and cerebrospinal fluid. It has important immunological properties, and is both antibacterial and antiviral. In particular, there is evidence that it can bind to at least some of the receptors used by coronaviruses and thereby block their entry. Of importance are Heparan Sulfate Proteoglycans (HSPGs) and the host receptor angiotensin-converting enzyme 2 (ACE2), as based on other activities lactoferrin might prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from attaching to the host cells. Lactoferrin (and more specifically enteric-coated LF because of increased bioavailability) may consequently be of preventive and therapeutic value during the present COVID-19 pandemic.

Topics: Angiotensin-Converting Enzyme 2; Animals; Anti-Bacterial Agents; Bacterial Infections; Dietary Supplements; Heparan Sulfate Proteoglycans; Humans; Lactoferrin; Peptidyl-Dipeptidase A; Receptors, Cell Surface; Receptors, Coronavirus; Receptors, Virus; Virus Diseases

Ascitic neutrophils from cirrhotic patients with spontaneous bacterial peritonitis (SBP) exhibit an impaired oxidative burst that could facilitate bacterial infection. However, the influence of the cell-free ascitic fluid of these patients on neutrophil function has not been investigated. To analyze this influence, we determined the ascitic levels of cytokines, resistin, and lactoferrin and their association with neutrophil function, disease severity score, and SBP resolution. We analyzed NETosis induction by microscopy and oxidative burst by the flow cytometry of healthy neutrophils cultured in ascitic fluid from cirrhotic patients with sterile ascites (SA) and with SBP before and after antibiotic treatment. Resistin, IL-6, IL-1 receptor antagonist, IL-1β, and lactoferrin levels were measured in ascitic fluids and supernatants of cultured neutrophils and PBMCs by ELISA. Upon stimulation, healthy neutrophils cultured in SBP ascitic fluid produced lower NETosis and oxidative burst than those cultured in SA. Ascitic resistin levels were negatively correlated with NETosis, oxidative burst, and ascitic glucose levels; and positively correlated with the model for end-stage liver disease score. After an E. coli or TNF-α stimulus, neutrophils were the major resistin producers. Resistin indirectly reduced the oxidative burst of neutrophils and directly reduced the inflammatory phenotype of monocytes and TNF-α production. Bacterial-induced resistin production can down-regulate the inflammatory response of macrophages and neutrophil function in ascitic fluid. Consequently, this down-regulation may jeopardize the elimination of bacteria that translocate to ascitic fluid in patients with cirrhosis.

Topics: Aged; Anti-Bacterial Agents; Ascites; Ascitic Fluid; Bacterial Infections; Cytokines; Extracellular Traps; Female; Glucose; Humans; Immunity, Innate; Interleukin-1beta; Interleukin-6; Lactoferrin; Liver Cirrhosis; Macrophages; Male; Middle Aged; Monocytes; Neutrophils; Peritonitis; Resistin; Respiratory Burst; Severity of Illness Index; Up-Regulation

Bacterial infections of the respiratory tract contribute to exacerbations and disease progression in chronic obstructive pulmonary disease (COPD). There is also an increased risk of invasive pneumococcal disease in COPD. The underlying mechanisms are not fully understood but include impaired mucociliary clearance and structural remodeling of the airways. In addition, antimicrobial proteins that are constitutively expressed or induced during inflammatory conditions are an important part of the airway innate host defense. In the present study, we show that osteopontin (OPN), a multifunctional glycoprotein that is highly upregulated in the airways of COPD patients co-localizes with several antimicrobial proteins expressed in the airways. In vitro, OPN bound lactoferrin, secretory leukocyte peptidase inhibitor (SLPI), midkine, human beta defensin-3 (hBD-3), and thymic stromal lymphopoietin (TSLP) but showed low or no affinity for lysozyme and LL-37. Binding of OPN impaired the antibacterial activity against the important bacterial pathogens Streptococcus pneumoniae and Pseudomonas aeruginosa. Interestingly, OPN reduced lysozyme-induced killing of S. pneumoniae, a finding that could be explained by binding of OPN to the bacterial surface, thereby shielding the bacteria. A fragment of OPN generated by elastase of P. aeruginosa retained some inhibitory effect. Some antimicrobial proteins have additional functions. However, the muramidase-activity of lysozyme and the protease inhibitory function of SLPI were not affected by OPN. Taken together, OPN can contribute to the impairment of innate host defense by interfering with the function of antimicrobial proteins, thus increasing the vulnerability to acquire infections during COPD.

Topics: Bacterial Infections; beta-Defensins; Cytokines; Humans; Lactoferrin; Lung; Midkine; Osteopontin; Protein Binding; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Secretory Leukocyte Peptidase Inhibitor; Streptococcus pneumoniae; Thymic Stromal Lymphopoietin; Treatment Failure; Up-Regulation

Although elevated levels of lactoferrin provide a biomarker for inflammatory bowel diseases and colorectal cancer, the clinical significance of these elevated levels in ascitic fluid of patients with ascites caused by liver cirrhosis is limited. The aims of our study were to investigate the usefulness of ascitic fluid lactoferrin levels for the diagnosis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and to evaluate the association between lactoferrin levels and the development of hepatocellular carcinoma (HCC).. A total of 102 patients with ascites caused by cirrhosis were consecutively enrolled into the study, from December 2008 to December 2011. Ascitic fluid lactoferrin levels were quantified using a human lactoferrin enzyme-linked immunosorbent assay kit.. The median ascitic fluid lactoferrin levels were significantly higher in patients with SBP than in those without SBP (112.7 ng/mL vs. 0.6 ng/mL; p < 0.001). The area under the receiver operator characteristic curve for the diagnosis of SBP was 0.898 (95 % confidence interval, 0.839-0.957, p < 0.001), with a sensitivity and specificity for a cut-off level of 51.4 ng/mL of 95.8 % and 74.4 %, respectively. Moreover, the incidence of HCC in the 78 patients without SBP was significantly higher in patients with high ascitic fluid lactoferrin levels (≥35 ng/mL) than in those with low ascitic fluid lactoferrin level (<35 ng/mL).. Ascitic fluid lactoferrin level can be a useful diagnostic tool to identify SBP in patients with ascites caused by cirrhosis. Elevated ascitic fluid lactoferrin level in patients without SBP may be indicative of a developing hepatocellular carcinoma.

Topics: Area Under Curve; Ascites; Ascitic Fluid; Bacterial Infections; Biomarkers; Carcinoma, Hepatocellular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Incidence; Lactoferrin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Peritonitis; Predictive Value of Tests; Prospective Studies; ROC Curve; Sensitivity and Specificity

The objective of the present work was to study the contribution of biofilms to the development of chronic bacterial rhinosinusitis. A total of 50 patients with this pathology were available for the examination. Mucosal swabs were taken from the middle nasal passages of all the patients to be used for the detection of biofilms by luminescence microscopy. The lactoferrine content in mucosal secretion from the nasal cavity was determined by an immunoenzymatic assay. Two groups of the patients presenting with bacterial rhinosinusitis were distinguished in the study of impression smears from nasal cavity mucosa by luminescence microscopy; one of them was comprised of biofilm-positive patients the other of biofilm-negative ones (56% and 44% respectively). The patients showing biofilms over nasal cavity mucosa had the lactoferrine content in mucosal secretion on the order of 0.0033±0.0008 mg/l compared with 0.0068±0.00075 mg/l in the biofilm-negative patients and 0.55±0.0005 mg/l in the healthy volunteers (controls). In other words, the biofilm-positive patients presenting with chronic bacterial rhinosinusitis had two times lower content of lactoferrine in mucosal secretion from the middle nasal passages than those in the biofilm negative group and 126 times lower content of lactoferrine than in the control group.

Topics: Adolescent; Adult; Bacterial Infections; Biofilms; Chronic Disease; Female; Humans; Lactoferrin; Male; Middle Aged; Nasal Mucosa; Rhinitis; Sinusitis; Young Adult

This study evaluates potential markers in blood and stools for their ability to distinguish bacterial from viral gastroenteritis. A total of 108 patients were prospectively recruited, of which 27 showed bacterial, 30 viral, and 51 no detectable pathogen, respectively. Cytokines, C-reactive protein (CRP), and white blood cells as well as the 2 fecal markers lactoferrin and calprotectin were determined. Statistics comprised Kruskal-Wallis test and U test in addition to an assessment of receiver operating characteristic. Interferon γ (IFNγ) levels were significantly increased in the viral group compared to the bacterial and nonspecific group. For the bacterial group, both fecal markers lactoferrin and calprotectin as well as CRP were significantly higher in comparison to the other 2 groups. To differentiate between bacterial and viral gastroenteritis, CRP, serum IFNγ, and the fecal proteins lactoferrin and calprotectin may be useful. A corresponding algorithm should be evaluated prospectively.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Blood Chemical Analysis; C-Reactive Protein; Cytokines; Diagnosis, Differential; Feces; Female; Gastroenteritis; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Virus Diseases

Decreased Toll-like receptor 2 (TLR2) expression has been reported in patients with chronic obstructive pulmonary disease and in a murine asthma model, which may predispose the hosts to bacterial infections, leading to disease exacerbations. Since airway epithelial cells serve as the first line of respiratory mucosal defense, the present study aimed to reveal the role of airway epithelial TLR2 signaling to lung bacterial [i.e., Mycoplasma pneumoniae (Mp)] clearance. In vivo TLR2 gene transfer via intranasal inoculation of adenoviral vector was performed to reconstitute TLR2 expression in airway epithelium of TLR2(-/-) BALB/c mice, with or without ensuing Mp infection. TLR2 and lactotransferrin (LTF) expression in airway epithelial cells and lung Mp load were assessed. Adenovirus-mediated TLR2 gene transfer to airway epithelial cells of TLR2(-/-) mice reconstituted 30-40% TLR2 expression compared with TLR2(+/+) cells. Such airway epithelial TLR2 reconstitution in TLR2(-/-) mice significantly reduced lung Mp load (an appropriate 45% reduction), coupled with elevated LTF expression. LTF expression in mice was shown to be mainly dependent on TLR2 signaling in response to Mp infection. Exogenous human LTF protein dose-dependently decreased lung bacterial load in Mp-infected TLR2(-/-) mice. In addition, human LTF protein directly dose-dependently decreased Mp levels in vitro. These data indicate that reconstitution of airway epithelial TLR2 signaling in TLR2(-/-) mice significantly restores lung defense against bacteria (e.g., Mp) via increased lung antimicrobial protein LTF production. Our findings may offer a deliverable approach to attenuate bacterial infections in airways of asthma or chronic obstructive pulmonary disease patients with impaired TLR2 function.

Topics: Adenoviridae; Animals; Bacterial Infections; Bacterial Load; Epithelial Cells; Gene Expression Regulation; Gene Transfer Techniques; Humans; Lactoferrin; Lung; Mice; Mice, Inbred BALB C; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Toll-Like Receptor 2

Nosocomial infection with antibiotic-resistant strains is a major threat to critical care medicine. Selective decontamination of the digestive tract (SDD) is one of the strategies used to reduce ventilator-associated pneumonia and sepsis in critically ill patients. In the present study, we performed pathogenic challenges of the digestive tract in a transgenic milk-fed animal model to test whether porcine lactoferrin (pLF) is an effective SDD regimen.. Transgenic mice expressing recombinant pLF in their milk at a mean+/-SD concentration of 120+/-13.6 mg/L during the lactation stage fed normal CD-1 mice pups for 4 weeks. The pups were subsequently challenged with pathogenic Escherichia coli, Staphylococcus aureus, and Candida albicans.. Compared with the control groups fed wild-type (normal) milk, the groups fed pLF-enriched milk demonstrated statistically significant improvements in weight gain; lower bacterial numbers in intestinal fluid, blood, and liver; healthier microvilli in the small intestine; and alveoli in the lungs.. Our results showed that oral administration of pLF-enriched milk to mice led to broad-spectrum antimicrobial activity in the digestive tract and protected the mucosa of the small intestine from injury, implying that pLF can be used as an effective SDD regimen.

Topics: Animals; Animals, Newborn; Bacteremia; Bacterial Infections; Body Weight; Candidiasis; Cytokines; Escherichia coli Infections; Gastrointestinal Tract; Immunohistochemistry; Intestines; Lactation; Lactoferrin; Lung; Mice; Mice, Transgenic; Milk; Polymerase Chain Reaction; Recombinant Proteins; Staphylococcal Infections; Swine

Canine leukocyte adhesion deficiency (CLAD) in Irish setters is caused by genetic defects of leukocyte integrin CD18 leading to recurrent bacterial infections. We report clinical features and analysis of neutrophil function from two mixed-breed canine littermates (one female and one male dog) similar to CLAD. The symptoms of pyogenic infection were first recognized at 3 months of age and since then the patients suffered from recurrent bacterial infections. These clinical findings were strongly suggestive of genetic phagocyte dysfunction. Neutrophil function tests revealed a marked reduction of serum-opsonized zymosan-mediated superoxide production in the two littermates. Neutrophils of the male dog revealed impaired integrin-mediated adherence and phagocytic activity, whereas ability of serum opsonization was normal. There was also a profound decrease of surface expression of CD11b/CD18 and beta2-integrin transcript level, detected by real-time RT-PCR without missense mutations unlike CLAD. Immunoblot analysis indicated that protein expression of cytochrome b(558) component gp91(phox), the cytosolic components p47(phox) and p67(phox) of NADPH oxidase components increased profoundly in the male. Our study suggests that decreased transcriptional levels of beta2-integrin without mutations, lead to downregulation of surface expression, resulting in multiple defects in adhesion-related neutrophil functions and consequently, recurrent bacterial infections from puppyhood.

Topics: Animals; Bacterial Infections; Base Sequence; CD11b Antigen; CD18 Antigens; DNA Primers; Dog Diseases; Dogs; Down-Regulation; Female; In Vitro Techniques; Lactoferrin; Leukocyte-Adhesion Deficiency Syndrome; Male; Mutation; NADPH Oxidases; Neutrophils; RNA, Messenger

The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This procedure is operator-dependent and lysis of PMNs during transport to the laboratory may lead to false-negative results. Furthermore, ascitic fluid culture is insensitive and leads to delays in diagnosis. The aim of this study was to assess the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to identify a cut-off level that can be used for future development of a rapid bedside test.. A total of 218 consecutive ascites samples from 148 patients (1-8 samples per patient) with cirrhosis at 2 tertiary care medical centers were examined for PMN count, bedside culture, and lactoferrin concentration. AFLAC concentrations were determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or greater with or without a positive culture was used for diagnosis of SBP.. Twenty-two (10.1%) samples fulfilled diagnostic criteria for SBP. Samples with SBP had a significantly higher lactoferrin concentration (median, 3744 ng/mL; 25th-75th percentiles [P25-P75], 788-9617) compared with non-SBP samples (median, 31 ng/mL; P25-P75, 12-67; P < .001). By using a cut-off level of 242 ng/mL, the sensitivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%, respectively. The area under the receiver operating characteristic curve was 0.98.. AFLAC can serve as a sensitive and specific test for diagnosis of SBP. Qualitative bedside assays for the measurement of AFLAC can be developed easily and may serve as a rapid and reliable screening tool for SBP in patients with cirrhosis.

Topics: Ascitic Fluid; Bacterial Infections; Biomarkers; Humans; Lactoferrin; Leukocyte Count; Liver Cirrhosis; Neutrophils; Peritonitis; Sensitivity and Specificity

Topics: Ascitic Fluid; Bacterial Infections; Biomarkers; Humans; Lactoferrin; Paracentesis; Peritonitis; Reagent Strips; Sensitivity and Specificity

Every year, about 2.2 million deaths occur worldwide due to diarrhea. Reliable diagnosis of patients with acute infectious diarrhea remains a formidable challenge to the clinicians. This is the first study reporting use of fecal calprotectin in diagnosing acute diarrhea. The aim was to compare the diagnostic accuracy of fecal calprotectin, fecal lactoferrin, and guaiac-based fecal occult blood test in a diverse group of consecutive patients with acute diarrhea in which routine bacterial stool cultures and cytotoxins for Clostridium difficile were performed.. This was a prospective case-control multicenter study from January 2004 until October 2007 in 2383 consecutive patients with acute diarrhea. They provided stool samples for performing cultures. Patients with positive cultures and an equal number of matched controls with negative cultures underwent fecal occult blood test and calprotectin and lactoferrin assays.. Calprotectin, lactoferrin, and fecal occult blood tests demonstrated sensitivity and specificity of 83% and 87%, 78% and 54%, and 38% and 85%, respectively, for diagnosing acute bacterial diarrhea.. Calprotectin showed high correlation with bacteriologically positive infectious diarrhea compared with lactoferrin and fecal occult blood test. It may potentially revolutionize management algorithm for patients with acute diarrhea. As a screening test, calprotectin can generate results within hours to support presumptive diagnosis of infectious diarrhea, which can decide suitability of stool samples for culture.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Case-Control Studies; Diarrhea; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Middle Aged; Occult Blood; Prospective Studies

Topics: Bacterial Infections; Female; Humans; Immunologic Factors; Infant; Infant, Newborn; Lactoferrin; Milk, Human

A 24-year-old woman suffering from post-influenza otitis media infection was initially treated with several series of a steroid (Elocon) and a combination of steroids and antibiotics (Atecortin, Dicortineff) without significant medical benefit. The isolated bacterial strains were identified as Staphylococcus homis and Staphylococcus epidermidis. Specific phage therapy applied sequentially over a period of three weeks resulted only in a partial reduction in inflammation and limited improvement in overall health condition. Oral application of lactoferrin (LF; 50-mg daily oral doses for seven days with two-week intervals) led to a complete clearance of both bacterial strains and full recovery of the patient. The recovery was associated with increased myelopoiesis and a sustained elevation of serum endogenous LF. In conclusion, specific bacteriophage therapy combined with the administration of lactoferrin proved to be effective in the treatment of antibiotic-resistant external ear infection.

Topics: Adult; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Drug Combinations; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fludrocortisone; Gramicidin; Humans; Lactoferrin; Neomycin; Otitis Media; Penicillin G; Staphylococcus epidermidis; Staphylococcus hominis; Treatment Outcome

The concentration of lactoferrin in bovine milk is dramatically increased in response to infection. The high levels of lactoferrin may have a role in the prevention of microbial infection of the mammary gland. However, molecular mechanisms of how the lactoferrin gene is regulated in the mammary gland in response to infection remain unknown. In this study, we isolated and characterized the 5' flanking region of the bovine lactoferrin gene. An 8.2 kilobase (kb) fragment of the bovine lactoferrin gene, containing 4.4 kb of 5' flanking region, exon 1, intron 1, and exon 2, was isolated from a bovine genomic library on two overlapping bacterial artificial chromosome (BAC) clones. Sequence analysis of the isolated lactoferrin gene revealed that the promoter region contains a high GC content, a non-canonical TATA box, multiple stimulating protein 1 (SP1)/GC elements, and other putative binding sites for transcription factors including nuclear factor-kappaB (NF-kappaB), activator protein 1 (AP1), signal transducer and activator of transcriptions 3 and 5 (STAT3 and STAT5), and steroid hormone receptors. To demonstrate that the isolated promoter is functional, 4.4 kb of 5' flanking region was inserted upstream from the firefly luciferase gene and the chimeric construct was transiently transfected into murine mammary epithelial cells. Transfection studies showed that the basal promoter activity is quite potent, being similar in strength to that of the simian virus 40 (SV40) promoter/enhancer. In addition, a 24-h treatment with Escherichia coli lipopolysaccharide (LPS) significantly stimulated its activity up to 2.3-fold in a dose-dependent manner. Furthermore, promoter deletion analysis indicated that the sequence up to -543 was sufficient for basal activity, whereas the sequence up to -1029 was required for maximal basal activity. The basal activity of the promoter is affected by both positive regulatory regions (-2462/-1879 and -1029/-75) and a negative regulatory region (-1407/-1029). LPS-responsive regions of the promoter were localized to the region from -1029 to -543 containing one STAT3 site and two NF-kappaB sites, and the region from -4355 to -2462 containing three AP1 sites and six NF-kappaB sites. Taken together, our findings suggested that the lactoferrin promoter responds to infection via the NF-kappaB pathway.

Topics: 5' Flanking Region; Amino Acid Sequence; Animals; Bacterial Infections; Base Sequence; Binding Sites; Blotting, Northern; Cattle; Cell Line; Cloning, Molecular; DNA; DNA-Binding Proteins; Dose-Response Relationship, Drug; Female; Gene Expression Profiling; Gene Expression Regulation; Lactoferrin; Lipopolysaccharides; Luciferases; Molecular Sequence Data; NF-kappa B; Promoter Regions, Genetic; Recombinant Fusion Proteins; Regulatory Sequences, Nucleic Acid; RNA, Messenger; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; STAT3 Transcription Factor; Trans-Activators; Transfection

Faecal lactoferrin, an iron-based glycoprotein found concentrated in secondary granules of neutrophils, may serve as a surrogate marker of inflammation in the intestine. We evaluated the usefulness of faecal lactoferrin as a predictor of infection with invasive enteropathogens in 262 children with diarrhoea. Lactoferrin at a dilution of 1:50 had the highest sensitivity for detection not only of conventionally cultured invasive enteropathogens but also of all other enteropathogens. Neither individual clinical symptoms nor the identification of faecal leucocytes by microscopy significantly predicted isolation of invasive enteropathogens from the faeces of children with diarrhoea. Faecal lactoferrin is a simple test which showed promise in predicting which children with diarrhoea are likely to be infected with invasive pathogens and can be incorporated as a screening test before faecal cultures are undertaken in this population.

Topics: Acute Disease; Bacterial Infections; Biomarkers; Child; Child, Preschool; Diarrhea; Escherichia coli Infections; Feces; Female; Humans; India; Infant; Lactoferrin; Leukocytes; Male; Predictive Value of Tests; Sensitivity and Specificity

Bacterial samples were obtained from the tonsillar surfaces of seven patients (four males, three females; median age 18 years, range 15 to 21 years) suffering from acute infectious mononucleosis with concomitant pharyngotonsillitis, and from five healthy controls. By using gold-labelled antiserum to human lysozyme and lactoferrin, micro-organisms on the tonsillar surfaces coated with these antibacterial substances could be identified by tracing the gold particles in the transmission electron microscope. In healthy individuals, most of the bacteria were coated with lysozyme and significantly more bacteria were coated with lysozyme than with lactoferrin (p < 0.01). In patients there was a non-significant reduction in lysozyme-coating of the bacteria, whereas lactoferrin-coating was significantly increased (p < 0.01). Changes in the lysozyme and/or lactoferrin coating of the tonsillar surface bacteria on the palatine tonsils during infectious mononucleosis cannot explain the tendency to immense local bacterial colonization with commensals and proneness to bacterial penetration into the epithelial cells.

Topics: Adolescent; Adult; Bacteria; Bacterial Infections; Epstein-Barr Virus Infections; Female; Humans; Immunohistochemistry; Lactoferrin; Male; Muramidase; Palatine Tonsil; Statistics, Nonparametric; Tonsillitis

This study compared the possibilities and limitations of 99mTc-labeled synthetic peptides derived from two human antimicrobial peptides, namely, ubiquicidin (UBI) and lactoferrin (hLF), for the scintigraphic detection of bacterial and fungal infections in mice and rabbits. The rationale of our approach was that selected peptides accumulate in infected areas but not in sterile inflammatory lesions, because they bind preferentially to microorganisms. 99mTc-labeled human neutrophil peptides (defensins), ciprofloxacin, and human polyclonal IgG were included as control agents.. 99mTc-labeled peptides and control agents were injected intravenously into animals that had been injected intramuscularly 18 h earlier with multidrug-resistant Staphylococcus aureus, Klebsiella pneumoniae, or fluconazole-resistant Candida albicans. Sterile inflammatory sites were induced by the injection of heat-killed microorganisms or lipopolysaccharide (LPS) into the thigh muscle. Up to 4 h after injection, the accumulation of 99mTc-labeled compounds in the infected/inflamed thigh muscles was determined using scintigraphic techniques and radioactivity counts in dissected tissues.. Scintigraphy revealed that 99mTc-labeled peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and defensins, which showed preferential in vitro binding to microorganisms in a former study, accumulated at a significantly higher rate (P < 0.01) in bacterial and C. albicans infections in mice and rabbits than in inflamed tissues induced by heat-killed microorganisms or by LPS. No significant difference in the accumulation of 99mTc-labeled ciprofloxacin was observed between infected and sterile inflamed thigh muscles in mice.. 99mTc-labeled antimicrobial peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and defensins accumulate significantly in tissues infected with gram-positive and gram-negative bacteria and C. albicans. Significantly lower (P < 0.01) accumulation of these peptides occurs in sterile inflamed tissues. These data indicate that the peptides preferentially tag microorganisms at the site of infection, which is in agreement with their preferential binding to the microorganisms in vitro and in vivo. 99mTc-labeled ciprofloxacin does not distinguish between infections and sterile inflammatory lesions, which implies that its specificity for the detection of bacterial infections is not warranted.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Candidiasis; Ciprofloxacin; Defensins; Drug Resistance, Multiple; Immunoglobulin G; Inflammation; Klebsiella Infections; Lactoferrin; Male; Mice; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Ribosomal Proteins; Staphylococcal Infections; Staphylococcus aureus; Technetium

Unmethylated CpG dinucleotide motifs in bacterial DNA, as well as oligodeoxynucleotides (ODN) containing these motifs, are potent stimuli for many host immunological responses. These CpG motifs may enhance host responses to bacterial infection and are being examined as immune activators for therapeutic applications in cancer, allergy/asthma, and infectious diseases. However, little attention has been given to processes that down-modulate this response. The iron-binding protein lactoferrin is present at mucosal surfaces and at sites of infection. Since lactoferrin is known to bind DNA, we tested the hypothesis that lactoferrin will bind CpG-containing ODN and modulate their biological activity. Physiological concentrations of lactoferrin (regardless of iron content) rapidly bound CpG ODN. The related iron-binding protein transferrin lacked this capacity. ODN binding by lactoferrin did not require the presence of CpG motifs and was calcium independent. The process was inhibited by high salt, and the highly cationic N-terminal sequence of lactoferrin (lactoferricin B) was equivalent to lactoferrin in its ODN-binding ability, suggesting that ODN binding by lactoferrin occurs via charge-charge interaction. Heparin and bacterial LPS, known to bind to the lactoferricin component of lactoferrin, also inhibited ODN binding. Lactoferrin and lactoferricin B, but not transferrin, inhibited CpG ODN stimulation of CD86 expression in the human Ramos B cell line and decreased cellular uptake of ODN, a process required for CpG bioactivity. Lactoferrin binding of CpG-containing ODN may serve to modulate and terminate host response to these potent immunostimulatory molecules at mucosal surfaces and sites of bacterial infection.

Topics: Adjuvants, Immunologic; B-Lymphocytes; Bacterial Infections; Base Sequence; Cell Line; CpG Islands; DNA, Bacterial; Humans; Lactoferrin; Oligodeoxyribonucleotides; Protein Binding

Mastitis is a common complication of human lactation. We examined milk specimens from eight women with clinical mastitis to determine their content of anti-inflammatory components. Antioxidant activity (spontaneous cytochrome c reducing activity), selected pro-inflammatory cytokines (IL-6, IL-1beta), selected endogenous cytokine control molecules (sIL-6R, sIL-1RII, and sTNFRI), lactoferrin, Na(+):K(+) ratios, and milk bioactivities that cause shedding of sIL-1RII from human polymorphonuclear leukocytes (PMN), suppress PMN aggregation, and suppress PMN adherence responses were not increased compared to normal milks. Neither the bioactivities that deplete PMN intracellular Ca(2+) stores nor those that block Ca(2+) influx into fMLP-stimulated PMN were significantly increased in mastitis milks. In contrast, levels of TNFalpha, sTNFRII, and IL-1RA and bioactivities that cause shedding of sTNFRI from human PMN were significantly increased compared to normal milks. Mastitis milk has the same anti-inflammatory components and characteristics of normal milk, with elevations in selected components/activities that may help protect the nursing infant from developing clinical illness due to feeding on mastitis milk.

Topics: Adult; Antioxidants; Bacterial Infections; Breast Feeding; Calcium Signaling; Cell Adhesion; Cell Aggregation; Cytochrome c Group; Cytokines; Female; Humans; Infant; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Lactoferrin; Mastitis; Milk Proteins; Milk, Human; Neutrophils; Opsonin Proteins; Oxidation-Reduction; Potassium; Receptors, Interleukin-1; Receptors, Tumor Necrosis Factor; Sialoglycoproteins; Sodium; Staphylococcus aureus; Tumor Necrosis Factor-alpha

This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth.. Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at >/=37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score.. Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of >/=1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r =.51; P =.0001), sialidase activity (r =.38; P =.0001), and bacterial vaginosis (r =.38; P =.0001), were weakly related to fetal fibronectin (r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5. 5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4).. Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity.

Topics: Bacterial Infections; Biomarkers; Cervix Uteri; Female; Fibronectins; Glycoproteins; Humans; Lactoferrin; Neuraminidase; Obstetric Labor, Premature; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Vaginal Diseases

The aim of this study was to select technetium-99m labelled peptides that can discriminate between bacterial infections and sterile inflammations. For this purpose, we first assessed the binding of various 99mTc-labelled natural or synthetic peptides, which are based on the sequence of the human antimicrobial peptide ubiquicidin (UBI) or human lactoferrin (hLF), to bacteria and to leucocytes in vitro. In order to select peptides that preferentially bind to bacteria over host cells, radiolabelled peptides were injected into mice intraperitoneally infected with Klebsiella pneumoniae (K. pneumoniae) and the amount of radioactivity associated with the bacteria and with the leucocytes was quantitated. The next phase focussed on discrimination between bacterial infections and sterile inflammatory processes using 99mTc-labelled peptides in mice intramuscularly infected with various bacteria (e.g. multi-drug-resistant Staphylococcus aureus) and in animals that had been injected with lipopolysaccharides (LPS) of bacterial origin to create a sterile inflammatory process. Also, we studied the distribution of 99mTc-labelled UBI 29-41 and UBI 18-35 in rabbits having an experimental thigh muscle infection with K. pneumoniae and in rabbits injected with LPS. Based on the results of our in vitro and in vivo binding assays, two peptides, i.e. UBI 29-41 and UBI 18-35, were selected as possible candidates for infection imaging. The radiolabelled peptides can detect infections with both gram-positive and gram-negative bacteria in mice as early as 5-30 min after injection, with a target-to-non-target (T/NT) ratio between 2 and 3; maximum T/NT ratios were seen within 1 h after injection. In rabbits, high T/NT ratios (>5) for 99mTc-labelled UBI 29-41 were observed from 1 h after injection. No accumulation of the selected 99mTc-labelled UBI-derived peptides was observed in thighs of mice and rabbits previously injected with LPS. Scintigraphic investigation into the biodistribution of 99mTc-labelled UBI peptides revealed that these peptides were rapidly removed from the circulation by renal excretion. Similar data were observed for 99mTc-labelled defensin 1-3. Our data for 99mTc-labelled hLF and related peptides indicate that these compounds are less favourable for infection detection. Taken together, 99mTc-labelled UBI 18-35 and UBI 29-41 enable discrimination between bacterial infections and sterile inflammatory processes in both mice and rabbits. Based on their characteristics

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Defensins; Diagnosis, Differential; Humans; In Vitro Techniques; Inflammation; Klebsiella Infections; Lactoferrin; Lipopolysaccharides; Male; Mice; Protein Binding; Proteins; Rabbits; Radionuclide Imaging; Ribosomal Proteins; Technetium

To distinguish sinusitis from uncomplicated "colds," we examined lactoferrin and eosinophilic cationic protein (ECP) in nasal secretions. Lactoferrin titers were >/=1:400 in 4% of persons with uncomplicated colds and controls but in 79% of persons with sinusitis or purulent sputa. ECP levels were >200 ng/ml in 61% of persons with colds and >3,000 ng/ml in 62% of persons with sinusitis. Nasal lactoferrin helps distinguish sinusitis from colds.

Topics: Bacterial Infections; Blood Proteins; Common Cold; Community-Acquired Infections; Eosinophil Granule Proteins; Humans; Lactoferrin; Mucus; Nasal Mucosa; Rhinovirus; Ribonucleases; Sinusitis

Fever suggests the likelihood of severe microbial infection. Abnormal temperature, tachycardia, tachypnea, and abnormal white blood cell counts define the systemic inflammatory response syndrome (SIRS). In 300 hospitalized medical patients with fever, we determined clinical variables and procalcitonin, elastase-alpha1-antitrypsin, and lactoferrin levels in plasma. Of the patients, 71% had clinical infection (by clinical judgment) and 44% had microbial infection (by microbiological testing). SIRS occurred in 95%, and the 28-day mortality rate was 9%. The sensitivity for predicting microbial infection, bacteremia, and mortality was less but the specificity was greater for supranormal procalcitonin, elastase-alpha1-antitrypsin, and lactoferrin levels than for SIRS. The area under the receiver operating characteristic curve (AUC) for microbial infection was higher for procalcitonin and elastase-alpha1-antitrypsin levels than for clinical variables and lactoferrin level. The AUC for bacteremia was also higher for inflammatory factors (>0.70; P < .001) than for clinical variables. The AUC for mortality (P < .05) was 0.79 for the respiratory rate, 0.69 for elastase-alpha1-antitrypsin level, 0.65 for heart rate, 0.61 for procalcitonin level, and 0.60 for white blood cell count. In febrile medical patients, plasma procalcitonin and elastase-alpha1-antitrypsin levels may predict microbial infection and bacteremia better than (and mortality as well as) do clinical symptoms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Bacteremia; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Lactoferrin; Leukocyte Elastase; Male; Middle Aged; Predictive Value of Tests; Prognosis; Protein Precursors

Topics: Agglutination Tests; Bacterial Infections; Breast Feeding; Child; Child, Preschool; Developing Countries; Diarrhea, Infantile; Feces; Helminthiasis; Humans; Infant; Intestinal Diseases, Parasitic; Lactoferrin; Leukocytes; Nicaragua

Lactoferrin (Lf) has been found in most biological fluids including amniotic fluid and cervical mucoids in pregnant women, and released from neutrophils in response to the inflammation. As Lf possesses antimicrobial properties, it is widely considered to be an important component of the host defence against microbial infections. It is known that premature labor is caused by amniotic infection with the increase of prostaglandin production. High concentration of the inflammatory cytokines: interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) in the amniotic fluid has been known. However, changes of Lf in amniotic fluid with infection has not been reported. In the present study, Lf concentrations in amniotic fluid were measured under the intra-uterine infections state and the biological significance of Lf was investigated. The effects of Lf on the IL-6 and IL-6mRNA production in cultured amnion cells were also investigated. The concentrations of Lf and IL-6 in amniotic fluid with CAM were 8.76 +/- 0.65 micrograms/ml and 6.92 +/- 4.88 ng/ml (n = 28) respectively and both were significantly higher (p < 0.01) than those without CAM [0.86 +/- 0.81 microgram/ml and 0.34 +/- 0.25 ng/ml (n = 31)]. Significant positive correlation (r = 0.91, p < 0.01) between Lf and IL-6 levels in amniotic fluid was found. IL-6 production induced by lipopolysaccharide (LPS) (100 ng/ml) in cultured amnion cells was significantly inhibited (p < 0.05) under the physiological concentration of Lf in amnion. Total RNA was extracted from the amniotic cells by guianizine solution. RT-PCR procedure and product analysis were performed from one microgram aliquote of total RNA. beta-actin was used as an international standard and c-DNA samples were followed by 30 cycles of PCR. RT-PCR product of IL-6 mRNA was detected by Southern hybridization. Expression of IL-6 mRNA was inhibited by the addition of Lf. From the results, the possibility that Lf might suppress amniotic IL-6 production under the condition of amniotic infection is suggested. It is also suggested that Lf might act as self defence mechanism from intra-uterine infection.

Topics: Amnion; Amniotic Fluid; Bacterial Infections; Cells, Cultured; Female; Humans; Interleukin-6; Lactoferrin; Pregnancy; RNA, Messenger

1. Faecal excretion of the leucocyte primary granule component, myeloperoxidase, and of the secondary granule component, lactoferrin, were compared in inflammatory bowel disease and infective diarrhoea. 2. Faecal lactoferrin correlated with faecal myeloperoxidase in both inflammatory bowel disease (P = 0.0018; n = 32) and infective diarrhoea (P = 0.00013; n = 37), but inflammatory bowel disease was associated with a much higher faecal excretion of lactoferrin but lower excretion of myeloperoxidase than infective diarrhoea. As a consequence, the median ratio of lactoferrin/myeloperoxidase excretion (both expressed as ng/mg of protein) for inflammatory bowel disease was 7.5 (range 3.5-21.3) with similar values for ulcerative colitis (n = 18) and Crohn's disease (n = 14) compared with only 0.9 (range 0.4-2.3; P < 0.0001) for infective diarrhoea. In inflammatory bowel disease faecal lactoferrin and myeloperoxidase excretion remained increased even in clinical remission. 3. In subsequent immunohistochemical studies to assess the possible explanation for these findings, lactoferrin and myeloperoxidase were demonstrated within crypt abscesses and surface mucus, both in inflammatory bowel and in infective diarrhoea mucosal samples. There was a slight increase in the number of lactoferrin-containing cells in the mucosal samples from ulcerative colitis and in the submucosa of samples from Crohn's disease compared with infective diarrhoea, but these changes were not sufficient to account for the marked increase in faecal lactoferrin excretion in inflammatory bowel disease. 4. In all mucosal samples, including those from normal mucosa, lactoferrin was also shown to be contained within mast cells. 5. These results could best be explained by a different mechanism for leucocyte activation in inflammatory bowel disease compared with infective diarrhoea, and are compatible with selective secretion of secondary granule components, which include lactoferrin but not myeloperoxidase, as a result of leucocyte activation by N-formylated bacterial peptides in inflammatory bowel disease.

Topics: Bacterial Infections; Colitis, Ulcerative; Crohn Disease; Diarrhea; Feces; Humans; Immunohistochemistry; Inflammatory Bowel Diseases; Intestinal Mucosa; Lactoferrin; Lymphocyte Activation; Mast Cells; Peroxidase; Saliva

The Leuko-Test yielded a negative predictive value of 98.4% when it was used to screen 325 patients for inflammatory bacterial enteritis and a negative predictive value of 99.4% when it was used to screen 416 stool specimens for those from which enteric pathogens would likely be recovered when cultured. Neither microscopy for fecal leukocytes nor an assay for fecal occult blood, alone or in combination, allowed for the reliable detection of invasive bacterial enteritis or the reliable selection of specimens for culture. When positive in the Leuko-Test, specimens collected from patients after the third day of hospitalization did not yield enteric pathogens when the specimens were cultured, and specimens collected from inpatients within the first 3 days of hospitalization or from outpatients did not contain Clostridium difficile toxin A. As a screening test, the Leuko-Test has the ability to generate rapidly a result which can support the presumptive diagnosis of inflammatory bacterial enteritis or which can be used to determine the suitability of stool specimens for bacteriologic culture.

Topics: Bacterial Infections; Bacteriological Techniques; Diagnostic Errors; Enteritis; Evaluation Studies as Topic; Feces; Humans; Lactoferrin; Latex Fixation Tests; Leukocytes; Occult Blood; Sensitivity and Specificity

Because of its low yield in unselected specimens, stool culture is often cost ineffective. We tested 55 fecal samples from Fairfax Hospital (46 patients with diarrhea and 9 from controls without diarrhea) for lactoferrin by latex agglutination (LFLA) with the Leukotest (Techlab, Blacksburg, Va.) as a marker for inflammatory diarrhea. Of the 28 samples with Salmonella, Shigella, or Campylobacter infection, 93% had detectable fecal lactoferrin at > or = 1:50 (61% had LFLA titers of > or = 1:400), while 83% of 18 samples with rotavirus or no detectable pathogen were LFLA negative at a titer of 1:50 (100% were negative at 1:400). All 9 controls without diarrhea were LFLA negative at 1:50. The use of fecal lactoferrin to screen for inflammatory diarrhea selects specimens for which stool culture is fivefold more likely to yield an invasive bacterial pathogen (reducing the cost per positive result by over $800) and thus may greatly enhance a cost-effective approach to evaluating diarrheal illness.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bacteriological Techniques; Biomarkers; Case-Control Studies; Child; Child, Preschool; Cost-Benefit Analysis; Diagnostic Errors; Diarrhea; Feces; Gastroenteritis; Humans; Infant; Lactoferrin; Latex Fixation Tests; Middle Aged

Topics: Antibodies; Bacterial Infections; Female; Humans; Immunoglobulin A, Secretory; Infant, Newborn; Lactoferrin; Lymphocytes; Macrophages; Milk, Human; Muramidase; Neutrophils

To study the occurrence of antineutrophil cytoplasmic antibodies (ANCA) in reactive arthritis (ReA).. Sera from 22 patients with ReA were analyzed by ELISA for the presence of autoantibodies (IgG and IgA) against a proteinase-3 containing azurophilic granule extract ("alpha-antigen") from human polymorphonuclear leukocytes, myeloperoxidase (MPO), and lactoferrin (Lf), respectively. Rheumatoid factor (RF), antinuclear antibodies (ANA), and HLA-B27 were also tested. Erythrocyte sedimentation rate and serum levels of C-reactive protein were used to assess disease activity. The patients were divided into acute or chronic (> 1 year) disease.. 12/22 patients (55%) had IgG ANCA (7 had MPO ANCA, 8 had Lf ANCA, and 4 had alpha-ANCA). Eight patients (36%) had IgA ANCA. One serum was positive only for IgA ANCA. 18/21 patients (86%) were HLA-B27 positive, and none had RF or ANA. The triggering infection was Chlamydia trachomatis in 6 cases. Campylobacter jejuni in 6, Yersinia enterocolitica in 4. In 6 patients the causative microorganism could not be determined. ANCA was more prevalent in chronic disease (6/7, 82%) compared to acute (7/15, 47%). No obvious correlation was seen between ANCA and disease activity.. ANCA, predominantly those reacting with Lf and/or MPO preparations, are common in ReA.

Topics: Adult; Arthritis, Reactive; Autoantibodies; Bacterial Infections; Campylobacter; Chlamydia; Chronic Disease; Cytoplasm; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Lactoferrin; Male; Middle Aged; Neutrophils; Precipitating Factors; Prohibitins; Rheumatoid Factor; Serologic Tests; Yersinia

Serum granulocyte-colony stimulating factor (G-CSF) was measured with an ELISA method in patients with acute bacterial and viral infections, or with an atypical pneumonia. Before initiation of antibiotic treatment, G-CSF was found to be significantly increased (799 +/- 1501 ng/l) in sera from 34 patients with an acute bacterial infection compared with the 27 patients with a viral infection (58 +/- 34 ng/l; P < 0.001) and with the eight patients with an atypical pneumonia (60 +/- 33) ng/l; P < 0.001). No significant difference in G-CSF levels was seen between gram-positive and gram-negative bacterial infections. In septic shock, increased G-CSF levels were seen both in patients with leucocytosis and leucopenia. In uncomplicated bacterial infections, both G-CSF and IL-6 were increased on day 0, and decreased rapidly after initiation of antibacterial therapy and before the patients became afebrile. In bacterial infections on day 0, G-CSF levels correlated with mononuclear cells (rs = -0.62, P < 0.001), IL-6 (rs = 0.40, P < 0.05) and S-MPO (rs = -0.5, P < 0.01). In viral infections, G-CSF was correlated with mononuclear cells (rs = 0.41, P < 0.05), white blood cell counts (rs = 0.56, P < 0.01), neutrophils (rs = 0.41, P < 0.05) and CRP (rs = 0.47, P < 0.05). We conclude that G-CSF is rapidly raised in the blood in acute bacterial infections but not in acute viral infections or in infections with Mycoplasma pneumonia. Our results also support the theory that G-CSF is involved in the mechanisms of mobilization of neutrophils into the peripheral circulation.

Topics: Acute Disease; Bacterial Infections; C-Reactive Protein; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-6; Kinetics; Lactoferrin; Leukocyte Count; Peroxidase; Pneumonia, Mycoplasma; Virus Diseases

As one of the biodefense mechanisms, lactoferrin (LFN) in the secreta of female genital organ may be an interesting biological material in view of its antimicrobial activity. In the present study, we investigated antimicrobial activities of LFN and its combination with cefpodoxime proxetil (CPDX-PR), we also as evaluated clinical effect of CPDX-PR. The following results were obtained. 1. Antimicrobial activities of LFN were tested against 15 strains of 10 species of bacteria, and potent activities against Staphylococcus aureus 209P, Escherichia coli, Klebsiella pneumoniae and Proteus spp. were found. 2. In a concomitant use of LFN with CPDX-PR (a checkerboard method), synergistic actions were observed against S. aureus 209P, E. coli STf, K. pneumoniae 602 and Pseudomonas aeruginosa 1046, and additive actions against E. coli NIHJ and Providencia rettgeri 1603. In 3 strains, the MICs of CPDX-PR in the presence of LFN were reduced to < 1/64. 3. In the evaluation of clinical effect of CPDX-PR, efficacy rates were 53/57 (92.9%) in a patient group with infections. The incidence of adverse reaction was 0/57.

Topics: Bacteria; Bacterial Infections; Cefpodoxime Proxetil; Ceftizoxime; Drug Resistance, Microbial; Drug Synergism; Female; Genital Diseases, Female; Humans; Lactoferrin

Bacterial colonization of the tracheo-bronchial tree is common and an established risk factor for infection in ventilated newborns. Elastase, a highly active proteinase, and lactoferrin, an iron-binding protein and potential modulator of the inflammatory process, are both major constituents of either azurophilic or primary granules of neutrophilic granulocytes, released by activation of these cells during the inflammatory response. Since both elastase, complexed with its major inhibitor alpha 1-proteinase inhibitor (E alpha 1-Pl), and lactoferrin (Lf) are indicators of granulocyte activation during bacterial infection, they may indicate infectious inflammation at the tracheobronchial site. To study whether these substances in a single suction probe may serve this purpose, we obtained 82 tracheo-bronchial aspirates routinely from 16 ventilated newborns with a median gestational age of 31.5 (range, 25-39) weeks for laboratory analysis and bacterial cultures. Systemic inflammatory response by differential white blood cell count and C-reactive protein (CRP) was monitored simultaneously. The median E alpha 1-Pl level was significantly elevated in culture-positive aspirates (1,005 micrograms/L; range, less than 30-29,240 micrograms/L) in contrast to culture-negative samples (158 micrograms/L; range, less than 30-1,408 micrograms/L). In addition to a diagnostic sensitivity of 77%, E alpha 1-Pl offered a high specificity of 88%, a positive predictive value of 97%, and a negative predictive value of 73%. In contrast, median Lf concentration (10.6; range, 0.3-58.3 mg/L vs. 11.7; range, 1.6-158 mg/L) showed no correlation with culture results. Of the culture-positive aspirates 36% corresponded with systemic signs of an acute inflammatory response, such as elevated I/T-ratio and CRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; C-Reactive Protein; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Lactoferrin; Pancreatic Elastase; Protease Inhibitors; Respiration, Artificial; Suction; Trachea

Increased vasopermeability and vasodilation, presumably the result of endothelial perturbation, are considered among the basic pathogenetic mechanisms in septic shock. Neutrophils have been implicated as a source for mediators in endothelial injury. We measured elastase-alpha 1-antitrypsin (alpha 1AT) complexes and lactoferrin as markers for release of neutrophil granule contents in plasma from patients with sepsis on admission to the Intensive Care Unit, and we delineated the relationship of neutrophil activation to other inflammatory parameters and to hemodynamic and biochemical parameters. Levels of elastase-alpha 1AT and lactoferrin significantly correlated with each other (r = 0.58; p less than 0.008), and were increased (greater than 3.33 and 5 nmol/L, respectively) in 96% and 71% of the patients, respectively. Lactoferrin, but not elastase-alpha 1AT, correlated with the number of white blood cells (r = 0.38; p = 0.008). Elastase-alpha 1 AT levels were significantly higher (p = 0.008), whereas white blood cell counts were lower (p = 0.015) in patients with shock when compared with patients without abnormal blood pressure. Both elastase-alpha 1AT and lactoferrin levels correlated with lactate levels (r = 0.33; p = 0.024 and r = 0.30; p = 0.04), suggesting a role for neutrophil activation in the pathogenesis of hypoxygenation. In addition, elastase-alpha 1AT correlated with the concentrations of interleukin 6 (IL-6) (r = 0.46; p = 0.001) and C3a (r = 0.38; p = 0.009), suggesting that cytokines and complement may contribute to the degranulation of neutrophils in sepsis. Elastase-alpha 1AT complexes were inversely related to C1-inhibitor (r = -0.33; p = 0.028) and to platelet numbers (r = -0.42; p = 0.003). Levels of elastase-alpha 1AT complexes in plasma appeared to be of prognostic significance; levels were higher in 27 patients who died than in 21 patients who survived (p = 0.01). The mortality in 27 patients with concentrations below 10 nM was 37%, whereas it was 81% in 21 patients with higher levels. The overall mortality in this study was 56%. These results provide further evidence that activation and degranulation of neutrophils, induced by multiple agonists, are involved in the development of fatal complications in patients with sepsis.

Topics: alpha 1-Antitrypsin; Bacterial Infections; Hemodynamics; Humans; Lactoferrin; Neutrophils; Pancreatic Elastase; Prognosis; Radioimmunoassay

Typical alterations of the white blood cell count are often missed during the acute course of infectious diseases. Activiation and degranulation of granulocytes are followed by elevation of E alpha 1 PI and lactoferrin plasma concentrations under these conditions. The aim of our study was the evaluation of the diagnostic significance of these granulocyte parameters in relation with the absolute granulocyte count in infected pediatric patients. A total number of 106 patients at the age of 1 day to 16 years were studied. 25 children suffered from viral, 26 from localized and 23 from systemic bacterial infections, 32 children exhibiting no signs of infection served as controls. Results of the study are given as medians and ranges. Total granulocyte count was elevated above controls (4.8; 2.2-12.7/nl) only in patients with localized bacterial infections (13.3; 5.5-36.5/nl). E alpha 1 PI and lactoferrin plasma concentrations correlated well (r = 0.72) and were found to be significantly elevated in patients with localized bacterial infections (856; 363-4820 micrograms/l and 748; 206-2078 micrograms/l) and septicemia respectively (661; 256-2078 micrograms/l and 871; 160-9550 micrograms/l). A clearcut differentiation of septic and locally infected patients was given by the ratio of E alpha 1 PI and total granulocyte counts. Significantly elevated E alpha 1 PI concentrations of patients exhibiting viral infections (295; 86-690 micrograms/l) may suggest effective granulocyte activation under this condition. Finally we conclude that E alpha 1 PI and lactoferin plasma concentration related to total granulocyte counts in infected patients may serve as a helpful indicator of granulocyte activation during the acute course of the disease.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lactoferrin; Leukocyte Count; Male; Sepsis; Serine Proteinase Inhibitors; Serpins; Viremia; Virus Diseases

Immunoluminometric assays for lactoferrin and elastase-alpha 1-proteinase inhibitor complexes were developed using solid-phase methodology, which has already been published from this laboratory. The aim of the study was to develop a rapid method to see whether elevated granulocyte activity was present in the lung, as for example in neonatal sepsis. The lactoferrin assay gave reliable results within 30 minutes, the elastase-alpha 1-proteinase inhibitor complexes, within 5 hours. The correlation between both analytes was good, so that the lactoferrin assay could replace the elastase-alpha 1-proteinase inhibitor assay in emergency cases. The lactoferrin assay was used for rapid answer, the elastase-alpha 1-proteinase inhibitor complex assay for "fine" monitoring of the progress of the disease. Both assays could be used to measure concentrations in plasma or bronchoalveolar lavage using a 10 microliters sample. Plasma for the elastase-alpha 1-proteinase inhibitor complex determination had to be diluted 1:50 before being assayed. Only EDTA plasma was used in the assay, as either heparin plasma or serum resulted in granulocyte destruction, thus giving rise to elevated, and non-reproducible results. The results from bronchoalveolar lavage show an excellent correlation between elastase-alpha 1-proteinase inhibitor complexes and lactoferrin. No interference was seen from lipaemic or icteric plasma samples. Results from haemolytic samples i.e. where lysis of erythrocytes and leukocytes had occurred, had to be treated with care if no clinical indication of intravascular haemorrhage was present. The assays lend themselves to perinatal diagnosis, as the total volume of plasma or lavage needed is theoretically under 50 microliters, i.e. ethically acceptable for regular monitoring of neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: alpha 1-Antitrypsin; Bacterial Infections; Blood Proteins; Bronchoalveolar Lavage Fluid; Humans; Immunologic Techniques; Infant; Infant, Newborn; Lactoferrin; Lactoglobulins; Luminescent Measurements

Topics: Bacterial Infections; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Mucins; Tears

The importance of the mammary gland as a potential immunological organ is characterized in this literature survey by the following aspects: immunoglobulins in colostrum and mother's milk, immunological active cells in colostrum and mother's milk, nonspecific factors in the mother's milk. The importance of the early nursing is emphasized from the immunological point of view.

Topics: Antibody Formation; Antibody Specificity; Bacteria; Bacterial Infections; Colostrum; Complement System Proteins; Female; Humans; Immunity, Cellular; Immunoglobulin A, Secretory; Immunoglobulins; Infant, Newborn; Infections; Intestinal Absorption; Lactoferrin; Milk, Human; Pregnancy; Sepsis

Topics: Bacterial Infections; Clinical Enzyme Tests; Clinical Laboratory Techniques; Humans; Lactoferrin; Lactoglobulins; Neoplasms; Neutrophils; Peroxidase; Peroxidases; Reference Values

Bronchial secretions obtained during bronchoscopic examination of 60 children suffering from respiratory tract infections were studied for the concentration of immunoglobulins, anti-proteolytic factors, lactoferrin, and lysozyme. Eleven children having bronchial asthma without a history of chronic or recurrent infections of the respiratory tract were designated as a control. The results were analysed in relation to clinical diagnosis (chronic bronchitis, bronchitis, bronchiectasis) or to the local status of bronchial mucosa at the time of bronchoscopy (no inflammation, inflammation, inflammation with documented bacterial infection). The statistical analysis of the results revealed a decrease of lactoferrin and locally produced IgA in the group of children suffering from bronchitis and chronic bronchitis. Samples infected with Haemophilus species had significantly higher concentration of lactoferrin than any other group. Similarly, albumin in this group was higher than in the other group except that other bacteria were present. Samples infected with Haemophilus also had increased concentrations of S-IgA, IgG, and anti-proteolytic factors when compared with the group without local inflammation.

Topics: Bacterial Infections; Bronchi; Bronchitis; Child; Child, Preschool; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Lactoferrin; Mucus; Muramidase; Respiratory Tract Infections; Serum Albumin

The indigenous oropharyngeal microflora is complex and consists of many different aerobic and anaerobic microorganisms. Nonindigenous pathogenic microorganisms do not normally colonize the oropharynx due to several different defense mechanisms such as cell specific bacterial attachment, secretion of antibacterial substances and immunoglobulins. Also microbial interactions play an important role in the prevention of new colonization of the oropharynx. Suppression of the indigenous flora by antibiotics promote new colonization. Patients that are severely compromised by disease may be infected by colonizing microorganisms. At special risk are patients with low neutrophil count and patients that are prone to aspiration pneumonia. Thus new colonization should be prevented in such risk patients. Careful monitoring of systemic antimicrobial therapy is essential and decontamination of oropharynx with local antimicrobial agents may be of value.

Topics: Attachment Sites, Microbiological; Bacterial Infections; Clindamycin; Erythromycin; Humans; Immune Tolerance; Lactoferrin; Lactoperoxidase; Lysosomes; Neutropenia; Oropharynx; Pneumonia, Aspiration; Risk

Most infections reach man via the mucosal membranes, and more than half of the lymphoid system is found in connection with mucosae. The major antibodies found on mucous membranes are secretory IgA, which function primarily by binding microorganisms and thereby preventing their contact with the host tissues. The optimal mode of immunization to obtain a secretory IgA response is not well defined. Repeated mucosal exposure with antigen may result in oral tolerance, with decreasing circulating antibodies but a remaining secretory IgA response. The secretory IgA response is usually short-lived and can be difficult to boost. IgM as well as IgG antibodies may add to host defence at the mucosal level, but when engaged, they usually induce inflammation in host tissues. Analogues to bacterial receptors on mucosal epithelium may be present in exocrine secretions such as human milk. During an attack on the host, it is possible that such receptor analogues may aid in the prevention of attachment of bacteria to mucous membranes used as an initial site. A number of non-specific host factors support mucosal defence. One of them is lactoferrin. Lactoferrin deficiency seems to result in recurrent bacterial infections, suggesting its importance in normal host defence.

Topics: Antibody Formation; Antigens, Bacterial; Bacterial Infections; Epithelium; Humans; Immunity, Cellular; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Lactoferrin; Mucous Membrane; Receptors, Immunologic; Secretory Component

Topics: Animals; Bacteria; Bacterial Infections; Blood Bactericidal Activity; Carrier Proteins; Guinea Pigs; Haptoglobins; Heme; Hemoglobins; Hemolysis; Humans; Iron; Iron Chelating Agents; Iron-Binding Proteins; Lactoferrin; Mice; Rabbits; Transferrin; Transferrin-Binding Proteins

Serum lactoferrin concentrations were elevated in 22 out of 49 newborn infants with suspected and verified severe bacterial as well as viral infections, suggesting that this protein resembled an acute phase reactant. In the infants suspected of having septicemia, high concentrations of C-reactive protein appeared to indicate a severe bacterial infection. Like lactoferrin, however, haptoglobin, orosomucoid, alpha 1-antitrypsin and alpha 1-antichymotrypsin discriminated only poorly or not at all between infants with severe bacterial infections and those in which such infections were unlikely. Thus, serum CRP concentrations remained the most valuable of the acute phase reactants tested as an aid in ruling out septicemia in the neonatal period.

Topics: Acute Disease; Acute-Phase Proteins; Bacterial Infections; Blood Proteins; C-Reactive Protein; Humans; Immunoglobulin M; Infant, Newborn; Lactoferrin; Lactoglobulins; Sepsis

Serum levels of lactoferrin, lysozyme and myeloperoxidase have been established in 31 healthy children. On average, serum lactoferrin was 330 micrograms/1, serum lysozyme 1638 micrograms/1 and serum myeloperoxidase 174 micrograms/1. Serum myeloperoxidase was, on average, significantly higher in children than in adults (p = 0.01), whereas serum lactoferrin and serum lysozyme were equal to those of adults. In a group of infection-prone children (n = 31), both serum lactoferrin and serum myeloperoxidase, but not the serum lysozyme levels, were significantly lower (p less than 0.001 and p = 0.002, respectively) than those of the reference children in spite of normal intracellular contents and even somewhat higher peripheral blood polymorphonuclear counts. Based on the assumption that serum lactoferrin and serum myeloperoxidase reflect turnover and activity of neutrophil granulocytes, the findings could suggest reduction in these respects and could be one contributing factor to the high infection propensity of these children. Serum levels of the three proteins have also been measured in 10 children with suspected or various forms of manifest leukemia. It is suggested that the levels reflect turnover and stage of maturation of the myeloid and monocytic cells and could, therefore, aid in the understanding and diagnosis of these diseases.

Topics: Adolescent; Adult; Bacterial Infections; Cell Division; Child; Child, Preschool; Female; Humans; Infant; Lactoferrin; Lactoglobulins; Leukemia; Leukocyte Count; Leukocytes; Male; Muramidase; Peroxidase; Peroxidases; Probability

Serum iron levels drop during stress and infection in all orders of vertebrates. These alterations constitute a physiologic response that benefits the host by depriving the invading pathogens of nutritionally required iron. Within an iron-poor environment, multiplication rates of pathogens are significantly diminished. The coordinated alteration of fever and serum iron concentration works synergistically in slowing the pathogens' growth rate. Attempts by bacteria to tear iron from serum transferrin with siderophores, iron binding compounds may be blocked with host lactoferrins that have an even higher affinity for the iron. When these attempts to block acquisition of iron by pathogens are compromised by hematomas, hemolysis, or parenteral administration of iron, mortality from infections dramatically increase. This article reviews the experimental and clinical evidence which supports the importance of iron metabolism in host immunity.

Topics: Bacteria; Bacterial Infections; Body Temperature; Ceruloplasmin; Humans; Iron; Lactoferrin; Transferrin

The effects of season and variations in the prevalence of infectious disease on the concentrations and daily production of breast-milk immunoproteins were studied in 152 rural Gambian mothers and their children up to 26 months post-partum. IgA, IgG, IgM, C3, C4, lactoferrin, lysozyme and secretory component concentrations and breast-milk volumes were measured longitudinally over a six month period which encompassed dry and rainy seasons. No increase in the production of any immunoprotein was observed at the time of maximum prevalence of serious infectious diseases, especially diarrhoea, in the children. Enhanced secretion of certain immunoproteins was noted in mothers of children aged 9-18 months at the beginning of the rainy season. There was some evidence that this may have been associated with skin sepsis, particularly impetigo, in the children. The production of most immunoproteins fell during the rainy season. This was not the result of declining maternal food intakes as similar decreases were seen for women receiving a dietary supplement.

Topics: Bacterial Infections; Complement C3; Complement C4; Developing Countries; Female; Gambia; Humans; Immunoglobulins; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Lactation; Lactoferrin; Milk, Human; Muramidase; Mycoses; Pregnancy; Rural Population; Seasons; Secretory Component; Virus Diseases

A quantitative cytochemical study has been made, using scanning-integrating microdensitometry, of 1000 toxic granulation blood neutrophils from 20 infected patients, in comparison with 1250 normal blood neutrophils. Myeloid precursor cells in 10 normal marrows were also studied. Normal bone marrow granulocyte maturation was associated with a progressive decrease in azurophilic granule enzymes (myeloperoxidase, beta-glucuronidase, acid phosphatase, chloroacetate esterase), and also Alcian blue staining from acid mucosubstance, but an increase in the specific granule marker lactoferrin. Toxic granulation blood neutrophils showed minor changes in the enzyme content of their azurophilic and specific granules, consistent with cell immaturity, and an increase in acid mucosubstance in azurophilic granules. Abnormal maturation of azurophilic granules, with persistence of acid mucosubstance, is the likely explanation for the intense Romanowsky dye staining of the toxic granulation neutrophil.

Topics: Acute Disease; Bacterial Infections; Bone Marrow Cells; Cell Differentiation; Cytoplasmic Granules; Densitometry; Histocytochemistry; Humans; Lactoferrin; Leukocytosis; Lysosomes; Neutrophils

The CSF levels of lactoferrin, lysozyme, and beta 2-microglobulin (beta 2 mu) were measured in patients with evident, probable, or possible inflammatory CNS reactions and compared to those found in neurologically apparently healthy patients. Patients with viral CNS infections had significantly raised beta 2 mu and lysozyme levels but normal lactoferrin levels, indicating a local activation of lymphocytes and monocytes but not of granulocytes. Patients with bacterial CNS infections had significantly raised levels of all three cell markers, but the increase of lysozyme and lactoferrin was relatively more pronounced than that of beta 2 mu, indicating that the inflammatory response to bacterial agents is dominated by monocytes and granulocytes. Patients with primary or secondary malignant brain tumors were characterized by a moderate increase of beta 2 mu and a considerable increase in both lysozyme and lactoferrin, i.e., the same protein pattern as observed in bacterial CNS infection. The lysozyme levels were moderately increased in half the patients with benign cerebral tumors while the levels of beta 2 mu and lactoferrin were normal, indicating that benign and malignant brain tumors induce different local inflammatory CNS reactions. Half the patients with pituitary gland adenoma had elevated beta 2 mu and lysozyme levels but normal lactoferrin levels, suggesting that immunological mechanisms are associated with the adenoma development. Patients with MS had moderately but significantly raised CSF levels of beta 2 mu and lysozyme and a third of them also had raised levels of lactoferrin, a protein pattern suggesting a low-active inflammatory process in CNS involving mononuclears and granulocytes. A similar protein pattern was found in Guillain-Barré syndrome. In cerebrosarcoidosis we noted considerably increased lysozyme and beta 2 mu but normal lactoferrin levels, consistent with the idea that the sarcoid granuloma mass is dominated by monocytic inflammatory cells. The data obtained indicate a clinical value of lactoferrin, lysozyme, and beta 2 mu as differential indices of inflammatory cell reactions taking place in various CNS processes.

Topics: Adult; Albumins; Bacterial Infections; beta 2-Microglobulin; Beta-Globulins; Central Nervous System Diseases; Cerebrospinal Fluid Proteins; Female; Humans; Inflammation; Lactoferrin; Lactoglobulins; Male; Muramidase; Virus Diseases

Neutrophils from a boy suffering from recurrent infections were found to be totally deficient in specific granules when studied by electron microscopy. In contrast, myeloperoxidase-containing azurophil granules were increased in number. This deficiency of specific granules could be detected at the light-microscopic level using an immunocytochemical technique to demonstrate the absence of lactoferrin. Neutrophils also exhibited abnormal nuclear segmentation, nuclear clefts, an abnormally weak cytochemical reaction for alkaline phosphatase, and an increased number of mitochondria and ribosomes. Some granulocytic precursors were abnormal, and many of these cells were phagocytosed by macrophages in the bone marrow. Despite these multiple abnormalities and the history of severe pyogenic infection, the in vitro bactericidal capacity of the neutrophils was within normal limits, and normal degranulation of azurophil granules occurred following phagocytosis. The precise mechanism by which the deficiency of specific granules in this patient led to an enhanced in vivo susceptibility to infection therefore remains obscure. However, attention is drawn to the fact that in three previously described cases of specific granule deficiency a history of recurrent infections was present.

Topics: Bacterial Infections; Blood Cells; Bone Marrow; Child; Cytoplasmic Granules; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Male; Microscopy, Electron; Neutrophils; Recurrence; Staining and Labeling

The intraneutrophilic concentrations of lactoferrin, myeloperoxidase, collagenase and chymotrypsin-like cationic proteins were measured sequentially during acute bacterial infection. The serum levels of lactoferrin and myeloperoxidase were also followed as well as the 'eosinophil' cationic protein as a marker for eosinophil leucocytes. During the early course of infection there was a profound but reversible decrease of intraneutrophilic lactoferrin. The levels of cellular collagenase and chymotrypsin-like cationic proteins also tended to decrease reversibly during day 2-8 in most cases; myeloperoxidase levels were normal except for two cases. Serum myeloperoxidase and lactoferrin correlated with blood neutrophil counts. In spite of the absence of peripheral eosinophils the 'eosinophil' cationic proteins of serum were increased on the first day of infection, which may reflect increased eosinophil turnover.

Topics: Bacterial Infections; Blood Proteins; Chymotrypsin; Eosinophils; Granulocytes; Humans; Lactoferrin; Leukocyte Count; Leukocytes; Microbial Collagenase; Neutrophils; Peroxidase

The changes in intraneutrophilic and plasma concentrations of the three antibacterial proteins lysozyme, lactoferrin, and myeloperoxidase were studied sequentially during acute bacterial infection in nine patients. Intraneutrophilic concentrations of the three proteins were decreased by more than 50% during the 1st week of infection, followed by a slow increase over the following 2 weeks. Nadir values coincided with maximal toxic granulation of the neutrophils. The data suggest that neutrophilic granulocytes are deficient during early bacterial infection, possibly because of deficient synthesis of antibacterial proteins in the bone marrow, and that neutrophil toxic granulation is the visual counterpart of this defect. The plasma concentrations of the three proteins showed considerable differences: whereas plasma lysozyme did not show any sequential changes, plasma myeloperoxidase was high at the start of infection and quickly decreased towards normal values, and plasma lactoferrin, high in the first samples, showed a secondary peak 1 week after onset of disease, before normalization was seen. These differences may result from differences in the signals are specific for the individual antibacterial protein and not for the different types of neutrophil granules.

Topics: Adult; Aged; Bacterial Infections; Blood Bactericidal Activity; Humans; Lactoferrin; Lactoglobulins; Meningitis; Middle Aged; Muramidase; Neutrophils; Peroxidase; Peroxidases; Pneumococcal Infections; Time Factors

Topics: Age Factors; Anemia, Hypochromic; Bacteria; Bacterial Infections; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature, Diseases; Iron; Lactoferrin; Milk, Human

Topics: Animals; Bacteria; Bacterial Infections; Conalbumin; Fever; Fungi; Humans; Hydroxamic Acids; Immunity; Infections; Iron; Lactoferrin; Mycoses; Protein Binding; Transferrin

Topics: Anemia, Hypochromic; Animals; Bacteria; Bacterial Infections; Binding, Competitive; Fungi; Humans; Immunity; Iron; Lactoferrin; Protein Binding; RNA, Bacterial; Transferrin