lactoferrin and Peritonitis

The article analyzes the results of effect of combined and local cytokine- and ozone therapy on the indices of lipid peroxidation, endogenous intoxication and ferroproteins in 111 patients with diffuse peritonitis. It was shown, that combined sequential local and systemic cytokine and ozone therapy allows correcting the expression of endogenous intoxication and lipid peroxidation in diffuse peritonitis. This method suppresses an inflammation in the abdominal cavity. At the same time, it accelerates the elimination of intestine atony and thereby potentiates the possibilities of traditional methods of treatment.

Topics: Adjuvants, Immunologic; Cytokines; Drainage; Drug Administration Routes; Drug Monitoring; Drug Therapy, Combination; Endotoxemia; Ferritins; Humans; Lactoferrin; Laparotomy; Lipid Peroxidation; Oxidants, Photochemical; Ozone; Peristalsis; Peritoneal Lavage; Peritonitis; Postoperative Complications; Severity of Illness Index; Treatment Outcome

During the resolution of inflammation, macrophages engulf apoptotic polymorphonuclear cells (PMN) and can accumulate large numbers of their corpses. Here, we report that resolution phase macrophages acquire the neutrophil-derived glycoprotein lactoferrin (Lf) and fragments thereof

Topics: Animals; Apoptosis; Cattle; Cells, Cultured; Cytokines; Disease Models, Animal; Extracellular Traps; Female; Humans; Inflammation; Lactoferrin; Macrophages; Male; Mastitis, Bovine; Mice; Mice, Inbred C57BL; Neutrophils; Peptide Fragments; Peritonitis; Phagocytosis

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

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

Methicillin-resistant Staphylococcus aureus (MRSA) infection remains a serious hazard to global health. The use of immune modulatory therapy to combat infection is gaining an interest as a novel treatment alternative. Lactoferrin (LF), an iron binding protein with immune modulating properties, has the potential to modify the course of systemic MRSA infection. Specifically, LF is capable of limiting deleterious inflammatory responses while promoting the development of antigen specific T-cell activity. The efficacy of a novel recombinant mouse LF (rmLF) to protect against MRSA infection was examined in a mouse peritonitis model. BALB/c mice were infected with a lethal dose of MRSA and treated at 2h post-infection with rmLF. Effects of rmLF on MRSA-infected primary monocytes and granulocytes were analyzed for inflammatory mediators. The rmLF treated mice demonstrated a modest increase in survival of more than 24h, albeit with reduced bacteremia. Serum cytokines, IL-17 and IL-6, were significantly reduced post-challenge post-rmLF treatment. The rmLF led to a minor decrease in IL-1b, and a slight increase in TNF-a production. Preliminary investigation towards human clinical relevance was accomplished using human blood derived monocytes and granulocytes infected with MRSA and treated with homologous recombinant human LF (rhLF). Treatment with (rhLF) led to increased production of IFN-g and IL-2. The human cell studies also showed a concurrent decrease in TNF-a, IL-6, IL-1b, IL-12p40, and IL-10. These results indicate that the rmLF and rhLF have a high degree of overlap to modify inflammatory responses, although differences in activities were observed between the two heterologous recombinant molecules.

Topics: Animals; Bacterial Load; CHO Cells; Cricetulus; Cytokines; Granulocytes; Humans; Immunologic Factors; Lactoferrin; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Monocytes; Peritonitis; Recombinant Proteins; Spleen; Staphylococcal Infections

Topics: Ascitic Fluid; Erythrocyte Count; Erythrocytes; Health Care Costs; Humans; Lactoferrin; Leukocyte Count; Mass Screening; Neutrophils; Peritonitis; Sensitivity and Specificity

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

Human granulocytes release 25-30% of the granular neutral proteases, collagenase and elastase, to the exterior of the cell during phagocytosis of yeast cells or immune complexes. Similar amounts of myeloperoxidase and lactoferrin are released. Crossed immunoelectrophoresis demonstrated that collagenase and elastase released extracellularly formed complexes with serum alpha1-antitrypsin. The presence of alpha1-antitrypsin complexes with granulocyte collagenase and elastase were also demonstrated in inflammatory processes, e.g. in the peritoneal exudate of acute peritonitis. The reactivity of neutrophil proteases with natural plasma protease inhibitors must be considered in assessing the role of these proteases as the etiologic agent of tissue damage and degradation during the inflammatory process.

Topics: Acute Disease; alpha 1-Antitrypsin; Ascitic Fluid; Extracellular Space; Granulocytes; Humans; Immunoelectrophoresis; Lactoferrin; Leukocytes; Microbial Collagenase; Pancreatic Elastase; Peritonitis; Peroxidase; Phagocytosis