lactoferrin and Communicable-Diseases

Lactoferrin (Lf) is a glycoprotein of the primary innate immune-defense system of mammals present in milk and other mucosal secretions. This protein of the transferrin family has broad antimicrobial properties by depriving pathogens from iron, or disrupting their plasma membranes through its highly cationic charge. Noteworthy, Lf also exhibits immunomodulatory activities performing up- and down-regulation of innate and adaptive immune cells, contributing to the homeostasis in mucosal surfaces exposed to myriad of microbial agents, such as the gastrointestinal and respiratory tracts. Although the inflammatory process is essential for the control of invasive infectious agents, the development of an exacerbated or chronic inflammation results in tissue damage with life-threatening consequences. In this review, we highlight recent findings in in vitro and in vivo models of the gut, lung, oral cavity, mammary gland, and liver infections that provide experimental evidence supporting the therapeutic role of human and bovine Lf in promoting some parameters of inflammation and protecting against the deleterious effects of bacterial, viral, fungal and protozoan-associated inflammation. Thus, this new knowledge of Lf immunomodulation paves the way to more effective design of treatments that include native or synthetic Lf derivatives, which may be useful to reduce immune-mediated tissue damage in infectious diseases.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Communicable Diseases; Humans; Immunity, Innate; Immunologic Factors; Immunomodulation; Inflammation; Lactoferrin

Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve pediatric care. The aim of this study was to review all clinical studies of lactoferrin (LF) in children in an effort to determine which interventions may improve pediatric care or require further research. We conducted a systematic and critical review of published literature and found 19 clinical studies that have used human or bovine LF for different outcomes: iron metabolisms and anemia (6 studies), fecal flora (5 studies), enteric infections (3 studies), common pediatric illnesses (1 study), immunomodulation (3 studies), and neonatal sepsis (1 study). Although the efficacies have varied in each trial, the main finding of all published studies is the safety of the intervention. Protection against enteric infections and neonatal sepsis are the most likely biologically relevant activities of LF in children. Future studies on neonatal sepsis should answer critically important questions. If the data from these sepsis studies are proven to be correct, it will profoundly affect the treatment of low birth weight neonates and will aid in the reduction of child mortality worldwide.

Topics: Child; Child Health Services; Clinical Trials as Topic; Communicable Diseases; Feces; Gastrointestinal Diseases; Humans; Immunomodulation; Infant, Newborn; Iron Metabolism Disorders; Lactoferrin; Sepsis

Topics: Breast Feeding; Communicable Disease Control; Communicable Diseases; Food Hypersensitivity; Humans; Immunity, Maternally-Acquired; Immunoglobulin A, Secretory; Immunoglobulin G; Infant, Newborn; Lactoferrin; Milk, Human; Time Factors

Topics: Animals; Anti-Infective Agents; Communicable Diseases; Humans; Iron; Lactoferrin

To evaluate the value of fecal leukocytes, fecal occult blood, fecal lactoferrin and combination of fecal leukocytes with clinical data in the workup of patients with inflammatory diarrhea.. A systematic literature search in all languages using MEDLINE (1970 to 1994), reference lists of articles primarily retrieved and of review articles and correspondence with experts in the field.. The search identified 2603 references, 81 of which were deemed relevant on the basis of prespecified selection criteria. Of these 25 contained sufficient data for further analysis and thus were finally included.. All data from the selected articles were extracted by one observer whereas the second reviewer checked these data for accuracy. True positive rates and false positive rates were calculated from each 2 x 2 table.. The study summarizes the diagnostic accuracy of the signaled tests as predictors of inflammatory diarrhea as defined by stool culture (the reference test). Plots of true positive rates against false positive rates demonstrated widely scattered points, indicating heterogeneity. A summary receiver operating characteristic curve was fitted to the data with the use of logistic transforms and weighted least squares linear regression. Of the 25 studies analyzed 38 data points were used to construct summary receiver operating characteristic curves for index tests.. Fecal lactoferrin was the most accurate index test. Fecal leukocytes showed the lowest performance as assessed by the area under the curve. Occult blood and combination of fecal leukocytes with clinical data yielded intermediate curves. A limited number of studies (fecal lactoferrin, and fecal leukocytes with clinical data) and methodologic flaws identified in the assessed studies must be solved in future primary studies to improve the usefulness of the metaanalytic approach used here.

Topics: Blood; Communicable Diseases; Diarrhea; False Negative Reactions; False Positive Reactions; Feces; Humans; Inflammation; Lactoferrin; Leukocytes

Topics: Antibody Formation; Antibody Specificity; Chemotaxis; Communicable Diseases; Humans; Hydrogen-Ion Concentration; Immunoglobulin A, Secretory; Interferons; Lactoferrin; Lymphocytes; Macrophages; Mucous Membrane; Phagocytosis; Skin

To investigate the effects of lactoferrin (LF) on infectious diseases in Japanese summer.. An intake of placebo, 200 mg, or 600 mg of LF were administered to healthy adults in Kyushu University of Health and Welfare for 12 weeks in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The primary endpoints were the prevalence and duration of infectious diseases and changes in immune parameters.. Three hundred and ten subjects were randomized (placebo, n = 104; 200 mg, n = 103; 600 mg, n = 103). Twenty subjects were lost to the follow-up, leaving 290 for a full analysis set (n = 99; n = 95; n = 96). The duration (day) of total infectious diseases was shorter in the 200 mg group (2.0, p = 0.045) and 600 mg group (2.0, p = 0.010) than in the placebo group (3.0). The duration of summer colds was shorter in the 600 mg group (2.0, p = 0.036) than in the placebo group (3.0). No significant differences were observed in the prevalence of infectious diseases or changes in immune parameters. In exploratory investigations, changes in the neutrophil phagocytic capacity, cortisol concentrations, and T score of "Vigor/Activity" in the Profile of Mood States 2 were greater in the 600 mg group than in the placebo group, when analysis was done on the lower half groups at the baseline. Adverse events were similar in each group and none had a causal relationship with the intake of the test foods.. In summer, the intake of LF attenuates infectious diseases, including summer colds.

Topics: Adult; Aged; Anti-Infective Agents; Common Cold; Communicable Diseases; Double-Blind Method; Female; Humans; Japan; Lactoferrin; Male; Middle Aged; Respiratory Tract Infections; Seasons; Treatment Outcome; Young Adult

Milk lactoferrin is a multi-functional, iron-binding glycoprotein with immunomodulatory effects, protecting infants against infectious diseases.. This study explored how maternal inflammation/infection and iron-deficiency anemia (IDA) might influence human milk lactoferrin. Lactoferrin might be elevated with maternal inflammation resulting from infectious disease processes. Conversely, lactoferrin might decrease with IDA, corresponding to scarce maternal iron for transfer in milk. In these two hypothesized scenarios, the degree of lactoferrin elevation or decrease might vary with infant vulnerability to infectious diseases or malnutrition. Alternatively, lactoferrin might be unassociated with inflammation/infection or IDA if mothers could buffer it against these conditions.. We used cross-sectional data from Ariaal mothers of northern Kenya (n = 200) to evaluate associations between milk lactoferrin and maternal inflammation/infection, IDA, infant age/sex, and the mother-infant variable interactions in multivariate regression models.. Maternal inflammation was associated with higher lactoferrin for younger infants (<~5 months of age) but with lower lactoferrin for older infants. Maternal IDA was unassociated with lactoferrin alone or in interaction with infant variables.. Results suggest that mothers of vulnerable young infants deliver more lactoferrin when they have inflammation/infection but mothers with older infants do not, and that maternal delivery of lactoferrin is unaffected by their IDA. Longitudinal research should verify these findings.

Topics: Anemia, Iron-Deficiency; Communicable Diseases; Cross-Sectional Studies; Female; Humans; Infant; Inflammation; Iron; Iron Deficiencies; Kenya; Lactoferrin; Milk, Human

To investigate whether immunologic factors in breast milk change in response to nursing infants' infection.. Total CD45 leukocyte count dropped from 5,655 (median and interquartile range: 1,911; 16,871) in the acute phase to 2,122 (672; 6,819) cells/ml milk after recovery with macrophage count decreasing from 1,220 (236; 3,973) to 300 (122; 945) cells/ml. Tumor necrosis factor-α (TNFα) levels decreased from 3.66 ± 1.68 to 2.91 ± 1.51 pg/ml. The decrease in lactoferrin levels was of borderline statistical significance. Such differences were not recorded in samples of the controls. Interleukin-10 levels decreased in the sick infants' breast milk after recovery, but also in the healthy controls, requiring further investigation. Secretory immunoglobulin A levels did not change significantly in the study or control group.. During active infection in nursing infants, the total number of white blood cells, specifically the number of macrophages, and TNFα levels increase in their mothers' breast milk. These results may support the dynamic nature of the immune defense provided by breastfeeding sick infants.. Breast milk from mothers of 31 infants, up to 3 months of age, who were hospitalized with fever, was sampled during active illness and recovery. Milk from mothers of 20 healthy infants served as controls.

Topics: Adult; Breast Feeding; Case-Control Studies; Chi-Square Distribution; Communicable Diseases; Female; Humans; Immunoglobulin A, Secretory; Infant; Infant, Newborn; Interleukin-10; Israel; Lactoferrin; Leukocyte Common Antigens; Leukocyte Count; Leukocytes; Macrophages; Male; Milk, Human; Tumor Necrosis Factor-alpha

In recent years, Lf has gained increasing interest as a result of its protective effects against a variety of diseases. While iron binding and interactions with mammalian receptors and microbial components are the best described mechanisms of action, recent studies have provided evidence that Lf properties may be related to immunoregulatory effects on Th1/Th2 cell activities. In vitro and in vivo experiments show that Lf is able to stimulate the differentiation of T cells from their immature precursors through the induction of the CD4 antigen. Studies performed under nonpathogenic conditions have shown distinct results with regard to the ability of Lf to support the proliferation and differentiation of Th cells into the Th1 or the Th2 phenotype. In addition, Lf plays different roles in diseases by affecting the Th1/Th2 cytokine balance in a manner dependent on the host's immune status. Thus, Lf could cause a Th1 polarization in diseases in which the ability to control infection or tumor relies on a strong Th1 response. Lf may also reduce the Th1 component to limit excessive inflammatory responses. Finally, Lf may provide protection against Th1- or Th2-induced diseases, such as autoimmune or allergic diseases, through correction of the Th1/Th2 imbalance.

Topics: Administration, Oral; Animals; Antibodies; Cell Differentiation; Cell Proliferation; Communicable Diseases; Cytokines; Inflammation; Lactoferrin; Mice; Mice, Inbred C57BL; Models, Biological; Th1 Cells; Th2 Cells; Toxoplasma

The aggregation of non-serotypable Haemophilus influenzae (NTHI) by whole saliva from patients with chronic obstructive lung disease (COLD) was investigated. Significant differences were observed between salivary aggregating activity of a control and COLD population (P < 0.001). Saliva from patients less prone to acute exacerbations had a greater capacity to aggregate bacteria compared with saliva from patients with a predilection to infection. The mechanism of saliva-mediated aggregation of NTHI was investigated and shown to be related to lysozyme content. Lysozyme activity in saliva was measured by the turbidimetric technique and results showed that patients with chronic bronchitis had increased levels of salivary lysozyme, with a subpopulation within the non-infection-prone group having greater amounts. A significant difference was observed in salivary lysozyme between controls and non-infection-prone (P < 0.005) and infection-prone (P < 0.05) patients, respectively: the non-infection-prone patients having significantly (P < 0.005) more than the infection-prone patients. There was significant correlation (r = 0.742, P < 0.001) between salivary aggregation of NTHI and lysozyme activity. Chromatographically purified human lysozyme had a similar aggregation profile to that of saliva. There was no difference in serum and saliva lactoferrin concentrations between groups, but there was a significant increase (P < 0.05) in serum lysozyme concentration in the non-infection-prone group. This study suggests that the level of salivary lysozyme derived from macrophages may play an important role in determining resistance or susceptibility to acute bronchitis.

Topics: Acute Disease; Adult; Aged; Bronchitis; Chronic Disease; Communicable Diseases; Female; Haemophilus influenzae; Humans; Inflammation; Lactoferrin; Lung Diseases, Obstructive; Macrophages; Male; Middle Aged; Monocytes; Muramidase; Neutrophils; Saliva; Salivation