lactoferrin and Infections

Iron is an essential trace metal for nearly all infectious microorganisms, and host defense mechanisms target this dependence to deprive microbes of iron. This review highlights mechanisms that are activated during infections to restrict iron on mucosal surfaces, in plasma and extracellular fluid, and within macrophages. Iron overload disorders, such as hereditary hemochromatosis or β-thalassemia, interfere with iron-restrictive host responses, and thereby cause increased susceptibility to infections with microbes that can exploit this vulnerability. Anemia of inflammation (formerly known as anemia of chronic diseases) is an "off-target" effect of host defense wherein inflammatory cytokines shorten erythrocyte lifespan by activating macrophages, prioritize leukocyte production in the marrow, and induce hepcidin to increase plasma transferrin saturation and the concentration of non-transferrin-bound iron.

Topics: Animals; Cation Transport Proteins; Cytokines; Disease Susceptibility; Hepcidins; Humans; Infections; Inflammation Mediators; Iron; Iron Deficiencies; Iron Overload; Lactoferrin; Leukocytes; Lipocalins; Macrophage Activation; Macrophages; Transferrin

Until relatively recently, the only significant source of lactoferrin in the diet was human lactoferrin, provided in breast milk. Today, however, bovine lactoferrin, isolated by dairy technology, as well as recombinant human lactoferrin are commercially available and can be added to foods and clinical products with perceived benefits to the consumer. In this review, the potential biological functions of dietary lactoferrin are described and critically examined.. Ingested lactoferrin has been suggested to exert antibacterial and antiviral activities in the intestine, in part through a direct effect on pathogens, but possibly also affecting mucosal immune function. The latter function is most likely mediated by lactoferrin being taken up by cells via a unique receptor-mediated pathway and affecting gene transcription. Lactoferrin has also been shown to enhance iron status of infants and pregnant women, possibly also via the receptor-mediated pathway. In addition, lactoferrin can stimulate intestinal cell proliferation and differentiation, causing expansion of tissue mass and absorptive capacity. On the contrary, lactoferrin has been shown to inhibit carcinogenesis. Recent findings also suggest that oral lactoferrin treatment may have an anti-inflammatory effect on pregnant women, reducing pregnancy complications.. Lactoferrin treatment may have beneficial preventive and therapeutic effects on infection, inflammation, and cancer as well as enhancing iron status and growth in vulnerable groups.

Topics: Anemia, Iron-Deficiency; Animals; Dietary Supplements; Female; Humans; Infant; Infections; Inflammation; Iron; Lactoferrin; Neoplasms; Pregnancy; Pregnancy Complications

Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family that is expressed and secreted by glandular cells and found in the secondary granules of neutrophils from which it is released in infected tissues and blood during the inflammatory process. Initially described as an iron-binding molecule with bacteriostatic properties, Lf is now known to be a multifunctional or multi-tasking protein. It is a major component of the innate immune system of mammals. Its protective effects range from direct anti-microbial activities against a large panel of microorganisms including bacteria, viruses, fungi, and parasites, to anti-inflammatory and anti-cancer activities. While iron chelation is central to some of the biological functions of Lf, other activities involve interactions of Lf with molecular and cellular components of both hosts and pathogens. Its powerful antimicrobial activities, immunomodulatory properties and prevention of septic shock, anti-carcinogenic functions and its growing importance in iron delivery and bone growth, combined with the data obtained either by in vivo studies or clinical trials, make this molecule and its derivatives very promising tools for health or nutritional applications.

Topics: Animals; Apoptosis; Blood Bactericidal Activity; Bone Remodeling; Cattle; Humans; Immunity, Innate; Infections; Inflammation; Intestinal Absorption; Iron, Dietary; Lactoferrin; Mammals; Models, Molecular; Neoplasms; Neovascularization, Physiologic; Protein Conformation

Human lactoferrin is a natural defense protein belonging to the innate immune system present in several body fluids and secretions, as well as in the secondary granules of polymorphonuclear neutrophils. Lactoferrin and its derivatives have pleiotropic functions including broad-spectrum anti-microbial activity, anti-tumor activity, regulation of cell growth and differentiation, and modulation of inflammatory as well as humoral and cellular immune responses. This is the reason why much research has addressed the potential therapeutic activity of these molecules in different clinical settings, especially regarding infectious diseases and uncontrolled inflammatory conditions. In patients with hematological malignancies treated with a hematopoietic stem cell transplantation (HSCT), morbidity and mortality due to infections and uncontrolled inflammation remains high, despite many advances in supportive care. These life-threatening complications are a result of the damage caused by the conditioning regimens to the mucosal barrier, and the innate and adaptive, humoral, and cellular immune defenses. These complications necessitate the continued exploration of new treatment modalities. Systemic and probably local levels of lactoferrin are decreased following HSCT. Therefore, the use of lactoferrin, or short peptide derivatives that retain the cationic N-terminal moiety that is essential for the anti-microbial and anti-inflammatory activity, may prove to be a promising versatile class of agents for managing the complications that arise from HSCT.

Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infections; Inflammation; Lactoferrin; Postoperative Complications; Transplantation Immunology

Despite recent advances in our understanding of the pathogenesis of enteric diseases, acute infectious diarrhea remains a major cause of morbidity and mortality worldwide. Infection is the most common cause of acute diarrhea. Some causes of infectious diarrhea also result in serious long-term sequelae such as hemolytic uremic syndrome, Guillain-Barré syndrome and malnutrition. A better understanding of bacterial pathogenesis has grown increasingly important because of the emergence of new pathogens and the growing problems of resistance among enteric pathogens and other enteric flora. Non-antimicrobial approaches to therapy have become increasingly important with the emergence of serious antimicrobial resistance, such as vancomycin-resistant enterococcal colonization of the gastrointestinal tract. Finally, new understanding of how intestinal bacteria cause disease is revealing that enteric infections might trigger damage to epithelial cells or the intestinal barrier, or disrupt intestinal barrier and absorptive function (without necessarily causing overt diarrhea); thus, enteric infections might be far more important as emerging causes of malnutrition than has been previously appreciated. Therefore, diarrhea is both a cause and an effect of malnutrition. Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration. Prevention of enteric illness by virtue of improved hygiene and provision of sanitation and water treatment is impractical in most developing countries, where morbidity and mortality rates are highest. For this reason, development of vaccines against the most important gastrointestinal infections remains a high priority.

Topics: Acute Disease; Diarrhea; Feces; Fluid Therapy; Humans; Infections; Lactoferrin; Polymerase Chain Reaction; Probiotics; Vaccines

Linkage between the central nervous system and the immune system is obvious and is accomplished through the hypothalamus-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes. This review focuses on the effects of psychic stress in animals and humans on immune system function. The effects of stress depend on its duration, type, and intensity. Generally, mild stress enhances the immune response. The effects of stress also depend on the animal's behavioral profile, genetic background and preexposure to stressful conditions. Prenatal stress modifies the immune response of the offspring. Stress also modifies autoimmune reactions in animals and humans. Knowledge of the mediators and their receptors involved in the functioning of the HPA and SAM axes allows pharmacological intervention to alleviate the harmful effects of stress on the immune system. Our studies revealed a benefit of oral lactoferrin application in reversing stress-induced changes in the humoral and cellular immune response in mice.

Topics: Administration, Oral; Animals; Antibody Formation; Autoimmunity; Female; Genetic Predisposition to Disease; Humans; Hypothalamo-Hypophyseal System; Immunity, Cellular; Infections; Lactoferrin; Nervous System; Pituitary-Adrenal System; Pregnancy; Prenatal Exposure Delayed Effects; Stress, Psychological

This review presents the state of the art of imaging of bacterial and fungal infections in laboratory animals using antimicrobial peptides labelled with technetium-99m ((99m)Tc). The mechanistic basis of this approach is that these peptides accumulate at sites of infection, but not in sterile inflammatory lesions, because of their preferential binding to bacteria and fungi over mammalian cells. For practical reasons, such as production of large amounts of peptides under good laboratory practice conditions and favourable pharmacokinetics, synthetic peptides representing such binding domains of natural antimicrobial peptides are preferred. On the basis of their preferential in vitro and in vivo binding to microorganisms over human cells, fast and easy penetration into the target area, and rapid clearance from the circulation via the urinary tract, various (99m)Tc-antimicrobial peptides were identified. Next, it was determined whether these radiopharmaceuticals distinguish infectious foci from sites of sterile inflammation. Further experiments with (99m)Tc-ubiquicidin-derived peptides in infected laboratory animals have revealed that the radioactivity at the infectious site correlated well with the number of viable bacteria present, indicating that these (99m)Tc-labelled peptides may enable the monitoring of the efficacy of antimicrobial therapy. Together, (99m)Tc-labelled synthetic peptides derived from human ubiquicidin are promising candidates for imaging of bacterial and fungal infections in nuclear medicine.

Topics: alpha-Defensins; Animals; Antimicrobial Cationic Peptides; Diagnosis, Differential; Humans; Infections; Lactoferrin; Metabolic Clearance Rate; Mice; Rabbits; Radioimmunodetection; Radiopharmaceuticals; Rats; Ribosomal Proteins; Technetium Compounds; Tissue Distribution

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: Anti-Infective Agents; Antibodies; Breast Feeding; Complement System Proteins; Humans; Infant; Infant, Newborn; Infections; Intestinal Mucosa; Lactoferrin; Lymphocytes; Milk, Human; Muramidase; Phagocytes

Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cytoplasmic Granules; Diagnosis, Differential; Frameshift Mutation; Humans; Immunologic Deficiency Syndromes; Infections; Lactoferrin; Neutrophils; Prognosis; Recurrence

Lactoferrin (LF) is an iron-binding protein found in milk and other secretory fluids of mammals as well as in secondary granules of neutrophils. Receptors for LF were detected and isolated on activated T and B cells, monocytes, intestinal brush border cells, platelets and neoplastic cells. Very low physiologic serum levels of LF increase significantly upon infection. Serum concentration of LF is also elevated in rheumatoid patients. It is suggested that the ability of LF to bind an excess of Fe() ions, needed for growth of microorganisms and tumors, represents an important defence mechanism in humans. LF, in addition, may contribute to the protection against pathogens and their metabolites by enhancing phagocytosis, cell adherence and controlling release of proinflammatory cytokines such as IL-1, IL-6 and TNF-alpha. The protein diminishes also damaging effects of free radical release. LF possesses interesting immunotropic properties with regard to immature T and B cells by promoting phenotypic and functional maturation of these cells. LF also controls the effector phase of cellular immune response and inhibits manifestations of autoimmune response in mice. One molecular form of LF with a ribonuclease activity may have a prognostic value in breast cancer. Lactoferrin may be potentially applied in neutropenic patients or in patients with bleeding disorders as a preoperative immunomodulator.

Topics: Adjuvants, Immunologic; Animals; Cell Adhesion; Cytokines; Humans; Immunity, Cellular; Infections; Lactoferrin; Mice; Neoplasms; Phagocytosis; Receptors, Cell Surface

A survey of recent knowledge on structure and importance of lactoferrin and ferritin is given. Lactoferrin is a symmetrically constructed glycoprotein which appears in the milk and in the body fluids and develops a bacteriostatic efficiency on account of the ability to Fe-binding together with other factors such as the IgA. In a particularly high concentration it is contained in the colostral milk of the woman. In the milk of the cattle the content is small. In the neutrophil granulocytes it is of importance for the functional ability in the phagocytosis. The ferritins are spherically constructed molecules which possess channels through which Fe-ions (up to 4,500 pro molecule) can be taken up or taken off. The ferritin content in the serum is correlated with the Fe-content of the liver and is dependent upon age as well as the Fe-supply. It decreases in Fe-deficiency: it increases in iron overload, in infectious diseases, in inflammation as well as in tumour development.

Topics: Animals; Ferritins; Humans; Infections; Lactoferrin; Lactoglobulins; Milk, Human; Phagocytosis; Structure-Activity Relationship; Transferrin

Topics: Biological Transport; Chelating Agents; Disease Susceptibility; Humans; Infections; Iron; Iron Deficiencies; Lactoferrin; Lymphocytes; Peritoneal Dialysis, Continuous Ambulatory; Protein Binding; Transferrin

Topics: Bacteria; Blood Bactericidal Activity; Carrier Proteins; Disease Susceptibility; Humans; Infections; Iron; Iron-Binding Proteins; Lactoferrin; Phagocytosis; Transferrin; Transferrin-Binding Proteins; Virulence

Topics: Animals; Conalbumin; Forecasting; Infection Control; Infections; Iron; Lactoferrin; Neoplasms; Transferrin; Vertebrates

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

An important component of nonspecific defense of vertebrates against microbial invasion is that of nutritional immunity. Hosts attempt to withhold growth-essential iron from invading bacteria, fungi, and protozoa. Clinical conditions in which hosts are stressed by excess quantities of iron in specific fluids, tissues, or cells result in enhanced susceptibility to infection. Methods for strengthening nutritional immunity are known in theory; research is needed to determine if these would be useful in clinical practice.

Topics: Animals; Erythropoiesis; Humans; Infant, Newborn; Infection Control; Infections; Iron; Lactoferrin; Protein Binding; Transferrin

Topics: Agammaglobulinemia; Anemia, Sickle Cell; Chemotaxis; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Immunity, Cellular; Immunoglobulin E; Immunologic Deficiency Syndromes; Infections; Job Syndrome; Lactoferrin; Leukocytes; Male; Muramidase; Opsonin Proteins; Peroxidase; Phagocytes; Phagocytosis; Staphylococcus

This paper discusses the nature of host resistance factors in human milk and epidemiologic studies regarding infections and mortality rates in breastfed and nonbreastfed babies. The defense factors and their proposed modes of action are: 1) a growth enhancer of lactobacilli, which interferes with intestinal colonization of enteric pathogens; 2) antistaphylococcal factors, which inhibit staphylococci; 3) secretory IgA and other immunoglobulins, which protect the gut and respiratory tract; 4) C4 and C3 (complement components; C3 fragments have opsonic, chemotactic, and anaphylatoxic activities); 5) lysozome, lysis of bacterial cell wall; 6) lactoperoxidase, killing of streptococci; 7) lactoferrin, kills microorganism by chelating iron, and 8) macrophages and lymphocytes, phagocytosis and cell-mediated immunity. Although it can be postulated that the breastfed infant's resistance to infection would be superior on account of the greater presence of these factors in human milk compared to cow's milk, little is known about the effects of these defense factors on the infant. Epidemiologic studies have reported on the lower morbidity and mortality rates of breastfed infants as compared to bottlefed infants. Other studies have focused on the protective effects of human milk upon the infant, but these have been inconclusive. In countries with poor sanitation and high infection rates, the incidence of bacterial infections is lowest in breastfed infants. The advantages of human milk however are difficult to demonstrate in societies with high standards of sanitation and low infection rates. Infection and mortality rates in infants have in fact declined in developed countries as the practice of breastfeeding declined. Until it is established that immunity to common pathogens is transmitted to the infant by human milk, it will not be known whether human milk does have protective effects.

Topics: Animals; Antibodies; Breast Feeding; Colostrum; Complement System Proteins; Escherichia coli; Fatty Acids; Growth Substances; Humans; Immunoglobulins; Infant; Infant, Newborn; Infections; Lactobacillus; Lactoferrin; Leukocytes; Mice; Milk, Human; Muramidase; Peroxidases; Staphylococcal Infections

Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications.. To determine whether or not enteral supplementation with bovine lactoferrin (The Tatua Cooperative Dairy Company Ltd, Morrinsville, New Zealand) reduces the risk of late-onset infection (acquired > 72 hours after birth) and other morbidity and mortality in very preterm infants.. Randomised, placebo-controlled, parallel-group trial. Randomisation was via a web-based portal and used an algorithm that minimised for recruitment site, weeks of gestation, sex and single versus multiple births.. UK neonatal units between May 2014 and September 2017.. Infants born at < 32 weeks' gestation and aged < 72 hours at trial enrolment.. Eligible infants were allocated individually (1 : 1 ratio) to receive enteral bovine lactoferrin (150 mg/kg/day; maximum 300 mg/day) or sucrose (British Sugar, Peterborough, UK) placebo (same dose) once daily from trial entry until a postmenstrual age of 34 weeks. Parents, caregivers and outcome assessors were unaware of group assignment.. Primary outcome - microbiologically confirmed or clinically suspected late-onset infection. Secondary outcomes - microbiologically confirmed infection; all-cause mortality; severe necrotising enterocolitis (NEC); retinopathy of prematurity (ROP); bronchopulmonary dysplasia (BPD); a composite of infection, NEC, ROP, BPD and mortality; days of receipt of antimicrobials until 34 weeks' postmenstrual age; length of stay in hospital; and length of stay in intensive care, high-dependency and special-care settings.. Of 2203 enrolled infants, primary outcome data were available for 2182 infants (99%). In the intervention group, 316 out of 1093 (28.9%) infants acquired a late-onset infection versus 334 out of 1089 (30.7%) infants in the control group [adjusted risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.04]. There were no significant differences in any secondary outcomes: microbiologically confirmed infection (RR 1.05, 99% CI 0.87 to 1.26), mortality (RR 1.05, 99% CI 0.66 to 1.68), NEC (RR 1.13, 99% CI 0.68 to 1.89), ROP (RR 0.89, 99% CI 0.62 to 1.28), BPD (RR 1.01, 99% CI 0.90 to 1.13), or a composite of infection, NEC, ROP, BPD and mortality (RR 1.01, 99% CI 0.94 to 1.08). There were no differences in the number of days of receipt of antimicrobials, length of stay in hospital, or length of stay in intensive care, high-dependency or special-care settings. There were 16 reports of serious adverse events for infants in the lactoferrin group and 10 for infants in the sucrose group.. Enteral supplementation with bovine lactoferrin does not reduce the incidence of infection, mortality or other morbidity in very preterm infants.. Increase the precision of the estimates of effect on rarer secondary outcomes by combining the data in a meta-analysis with data from other trials. A mechanistic study is being conducted in a subgroup of trial participants to explore whether or not lactoferrin supplementation affects the intestinal microbiome and metabolite profile of very preterm infants.. Current Controlled Trials ISRCTN88261002.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in

Topics: Animals; Cattle; Enteral Nutrition; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Infant, Extremely Premature; Infant, Premature, Diseases; Infections; Lactoferrin; Male

Recent work demonstrated a role for myeloid-derived suppressor cells (MDSCs) in the antimicrobial response in newborns, but the signals guiding their differentiation remained unknown. In this issue of the JCI, Liu et al. demonstrate that lactoferrin (LF) converts newborn neutrophils and monocytes to MDSCs via the low-density lipoprotein receptor-related protein-2 (LRP2) receptor and NF-κB activation. Due to their strong antimicrobial activity, adoptive transfer of MDSCs generated by in vitro culture with LF prolonged the survival of newborn mice with necrotizing enterocolitis, a severe pathology in preterm infants. These findings indicate a surprising protective role of MDSCs in newborns and demonstrate the potential of MDSC therapy for the treatment of infants with diseases associated with deregulated inflammation.

Topics: Animals; Animals, Newborn; Humans; Infant, Newborn; Infant, Premature; Infections; Lactoferrin; Mice; Myeloid-Derived Suppressor Cells

Neutrophil extracellular traps (NETs) are extracellular DNA filaments formed during neutrophil activation. This process, called netosis, was originally associated with neutrophil antibacterial properties. However, several lines of evidence now suggest a major role for netosis in thrombosis, autoimmune diseases, and cancer. We demonstrate here that highly purified human blood monocytes are also capable of extracellular trap (ET) release in response to several stimuli. Monocyte ETs display a morphology analogous to NETs and are associated with myeloperoxidase (MPO), lactoferrin (LF), citrullinated histones, and elastase. Monocyte ET release depends on oxidative burst but not on MPO activity, in contrast to neutrophils. Moreover, we demonstrate procoagulant activity for monocyte ETs, a feature that could be relevant to monocyte thrombogenic properties. This new cellular mechanism is likely to have implications in the multiple pathologic contexts where monocytes are implicated, such as inflammatory disorders, infection, or thrombosis.

Topics: Extracellular Traps; Histones; Humans; Infections; Inflammation; Lactoferrin; Monocytes; Pancreatic Elastase; Peroxidase; Thrombosis

Lactoferrin (LTF), an important first line defense molecule against infection, is a common target for humoral autoimmune reactions in humans. Since LTF is a multifunctional protein capable of activating innate immune cells via various surface receptors, we hypothesized that LTF-containing immune complexes (ICs) (LTF-ICs), likely formed in patients with high titer anti-LTF autoantibodies, could possess unique monocyte/macrophage-activating properties compared with other ICs. ELISA analysis on serum samples from rheumatoid arthritis (RA) patients (n = 80) and healthy controls (n = 35) for anti-LTF autoantibodies confirmed a positive correlation between circulating LTF-specific IgG and RA. ICs between human LTF and LTF-specific IgG purified from patient sera or immunized rabbits and mice, but not control ICs, LTF or Abs alone, elicited strong production of TNF-α and IL-1β by freshly fractionated human peripheral blood monocytes and monocytes-derived macrophages. Furthermore, LTF-ICs utilized both membrane-anchored CD14 and CD32a (FcγRIIa) to trigger monocyte activation in an internalization-, Toll-like receptor (TLR)4- and TLR9-dependent manner, and also that LTF-IC-induced cytokine production was blocked by specific inhibitors of caspase-1, NF-κB and MAPK. These results uncover a possible pathway for LTF-ICs perpetuating local inflammation and contributing to the pathogenesis of autoimmune diseases by triggering activation of infiltrating monocytes or tissue macrophages in vivo.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Anti-Idiotypic; Antigen-Antibody Complex; Arthritis, Rheumatoid; Autoantibodies; Autoimmunity; Female; Humans; Immunity, Humoral; Immunoglobulin G; Infections; Inflammation; Lactoferrin; Macrophages; Male; Middle Aged; Monocytes; Tumor Necrosis Factor-alpha

Topics: Anemia, Sickle Cell; Hemoglobin A; Hemoglobin, Sickle; Humans; Infections; Lactoferrin; Reference Values

Lactoferrin is an iron-binding protein with antimicrobial properties. This study was undertaken to determine whether amniotic fluid concentrations of this protein change with gestational age, infection, labor, and rupture of membranes.. This cross-sectional study included women who underwent transabdominal amniocentesis (n = 268) in the following groups: (1) mid trimester of pregnancy; (2) preterm labor who delivered at term, preterm labor who delivered preterm with intra-amniotic infection, and preterm labor who delivered preterm without intra-amniotic infection; (3) preterm premature rupture of membranes in the presence or absence of intra-amniotic infection; (4) term with intact membranes not in labor, in labor, and in labor with intra-amniotic infection; and (5) premature rupture of membranes at term not in labor. In addition, lactoferrin concentrations were determined in maternal plasma and cord blood of patients at term not in labor. Lactoferrin concentration was measured with an immunoassay.. (1) Lactoferrin was detectable in 85.4% (229/268) of amniotic fluid samples, not detectable in all fluid obtained in the mid trimester, and detectable in all maternal and cord plasma samples. (2) The concentration of lactoferrin increased with advancing gestational age (r = 0.68; P <.0001). (3) Intra-amniotic infection was associated with significant increases in amniotic fluid lactoferrin concentrations in patients with preterm labor (no intra-amniotic infection median, 1641.2 ng/mL; range, <1.24-35,090.0 ng/mL; vs intra-amniotic infection median, 3833.6 ng/mL; range, 746.0-47,020.0 ng/mL; P <.001), term labor (no intra-amniotic infection median, 2085.8 ng/mL; range, 425.0-23,230.0 ng/mL; vs intra-amniotic infection median, 5627.0 ng/mL; range, <1.24-19,220.0 ng/mL; P <. 001), and preterm premature rupture of membranes (no intra-amniotic infection median, 2190 ng/mL; range, <1.24-7456.1 ng/mL; vs intra-amniotic infection median, 3449.3 ng/mL; range, <1.24-83,600. 0; P <.01). (4) Spontaneous labor at term but not preterm was associated with a significant decrease in amniotic fluid lactoferrin concentration (P <.05). (5) Spontaneous term parturition was associated with a significant increase in umbilical cord plasma lactoferrin concentration (P <.005).. (1) Intra-amniotic infection was consistently associated with dramatically increased concentrations of lactoferrin in amniotic fluid. (2) Term parturition was associated with a significant increase in lactoferrin concentration in the fetal compartment (umbilical cord blood) and a decrease in the amniotic compartment. We propose that lactoferrin is part of the repertoire of host defense mechanisms against intra-amniotic infection.

Topics: Cross-Sectional Studies; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infections; Labor, Obstetric; Lactoferrin; Pregnancy; Ureaplasma Infections; Ureaplasma urealyticum; Uterine Diseases

Lactoferrin was analysed with an ELISA in pleural effusions from 21 patients with malignant exudative effusions (15 carcinomas and 6 mesotheliomas), 12 patients with non-malignant exudative effusions of unknown aetiology, 11 patients with transudative effusions due to congestive heart failure, 12 patients with exudative effusions secondary to infection, and 2 patients with tuberculous effusions. Median pleural fluid lactoferrin was 133 micrograms/l (range 25-435) in carcinomas, 55 micrograms/l (23-185) in mesotheliomas, 198 micrograms/l (31-530) in non-malignant exudates, 68 micrograms/l (17-205) in transudates, 1815 micrograms/l (1380-2050) in infectious exudates and 107 micrograms/l (88-125) in tuberculosis. Due to a wide overlap between the various groups pleural fluid lactoferrin appears to be of limited value in the routine diagnostic evaluation of non-infectious pleural effusions, but seems to separate infectious exudates from non-infectious exudates.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Infections; Lactoferrin; Male; Mesothelioma; Middle Aged; Pleural Effusion; Pleural Effusion, Malignant

To assess lactoferrin as a marker of infection, plasma lactoferrin (LF) levels were determined in elderly in patients with infection and compared with age- and sex-matched healthy and hospital controls and young healthy blood donors. The median LF level in infection (800 ng/mL) was significantly higher than in healthy elderly living in old people's home (300 ng/mL) or elderly hospital controls (298 ng/mL) (p less than 0.01 in each case). Plasma LF correlated significantly with elastase alpha-1-proteinase inhibitor complex (EPIC) (Rs = 0.8, p less than 0.01) and C-reactive protein (CRP) (Rs = 0.45, p less than 0.02), but not with erythrocyte sedimentation rate (ESR) or white blood cell counts. We conclude that plasma LF, like CRP and EPIC, is a marker of infection in elderly individuals.

Topics: Adult; Aged; Female; Humans; Infections; Lactoferrin; Leukocyte Elastase; Male; Pancreatic Elastase

Iron, iron-binding capacity, lactoferrin and total protein were determined in the plasma and pleural fluid of 30 patients with cardiac failure (n = 10), infectious/inflammatory disease (n = 9) and metastatic carcinoma (n = 11). In 16 patients pleural transferrin and ferritin was also measured. Plasma iron and total iron-binding capacity were reduced in inflammatory and neoplastic disease, whereas hyposideremia with normal iron-binding capacity was seen in patients with heart failure. Plasma lactoferrin was reduced in metastatic carcinoma. Exudates (protein greater than or equal to 30 g/l; infectious/inflammatory: 9/9, carcinomatous: 10/11) had significantly higher iron, lactoferrin, transferrin and ferritin concentrations than transudates (protein less than 30 g/l; heart failure: 10/10, carcinomatous: 1/11). Statistically, infectious/inflammatory exudates could be distinguished from neoplastic exudates by a higher median iron concentration (non-parametric Wilcoxon-Mann-Whitney test). Overlap of the respective ranges, however, did not allow a clear-cut differential diagnosis in individual cases. Pleural lactoferrin concentrations, on the other hand, correlated with the pleural granulocyte count and nonspecifically reflect the degree of granulocytic inflammation. Positive pleural/plasma correlations of protein and of iron concentrations were found in exudates only. Within exudates and transudates, on the other hand, total protein correlated with transferrin but not with iron concentrations. Therefore, and because of the substantially higher pleural/plasma ratio for iron than for transferrin concentrations, a quantitatively important, non-transferrin bound iron pool in pleural fluids, most probably ferritin, must be assumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Exudates and Transudates; Ferritins; Heart Failure; Humans; Infections; Iron; Lactoferrin; Metalloproteins; Neoplasms; Pleural Effusion; Transferrin

Plasma lactoferrin was measured within 24 h of birth in 23 preterm infants of between 24 and 36 weeks gestation. Lactoferrin concentrations fell with decreasing gestational age whilst the incidence of subsequent infection rose. Sequential measurements on a subgroup of 10 preterm infants showed that even when initial lactoferrin concentrations were within the range for term infants, they fell during the first week. Lactoferrin concentrations in preterm babies may rise transiently, such increases often being associated with clinical signs of infection. A rise in plasma lactoferrin of 200 micrograms/L or more over a period of less than 48 h is suggestive of infection. These findings are discussed in terms of both the possible role of lactoferrin, and the clinical usefulness of the measurement.

Topics: Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Lactoferrin; Lactoglobulins

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: Anemia; Anemia, Hypochromic; Humans; Infections; Intestine, Small; Iron; Lactoferrin; Lactoglobulins; Milk, Human; Neutrophils; Phagocytosis

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