Plasma Lipopolysaccharide-binding Protein Research Articles

Markers of intestinal permeability are already altered in early stages of non-alcoholic fatty liver disease: Studies in children.

Background & aimsRecent studies have shown that patients with manifest non-alcoholic fatty liver disease (NAFLD), e.g. steatosis grade 3 or steatohepatitis with or without beginning fibrosis frequently show altered fecal microbiota composition and elevated bacterial endotoxin levels. However, if these alterations are signs of a progressing disease or are already found in initial disease stages has not yet been clarified.MethodsTwenty children with simple steatosis (grade 1) diagnosed by ultrasound and 29 normal weight healthy control children (age <10 years) were included in the study (mean age 7.6 ± 1.1 years). Metabolic parameters, markers of intestinal barrier function and inflammation were determined.ResultsActivity of alanine aminotransferase, concentrations of some markers of inflammation and insulin resistance were significantly higher in plasma of NAFLD children than in controls. When compared to controls, plasma bacterial endotoxin and lipopolysaccharide-binding protein (LBP) levels were significantly higher in NAFLD children (+50% and +24%, respectively), while soluble CD14 serum and D-lactate plasma levels as well as the prevalence of small intestinal bacterial overgrowth did not differ between groups. Plasma endotoxin and LBP levels were positive associated with proinflammatory markers like plasminogen activator inhibitor-1, c-reactive protein, interleukin-6 and leptin while no associations with markers of insulin resistance were found.ConclusionsTaken together, our results indicate that even in juvenile patients with early stages of NAFLD e.g. simple steatosis grade 1, plasma endotoxin concentrations are already elevated further suggesting that intestinal barrier dysfunction might be present already in the initial phases of the disease.

Effects of proportion of cassava and lactic acid-treated cassava in rations on rumen pH and plasma lipopolysaccharide-binding protein in beef cattle

Effects of proportion of cassava and lactic acid-treated cassava in rations on rumen pH and plasma lipopolysaccharide-binding protein in beef cattle

Post-Effect of Air Quality Improvement on Biomarkers for Systemic Inflammation and Microparticles in Asthma Patients After the 2008 Beijing Olympic Games: a Pilot Study.

This study's aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1. The number of circulating endothelial cell-derived microparticles was significantly lower during the phase 2 than that during phase 1 in asthma patients. The level of plasma lipopolysaccharide-binding protein (LBP) was significantly decreased in asthmatics in phase 2. The level of norepinephrine was significantly higher in phase 2 than that in phase 1 in plasma from both asthma patients and healthy subjects. There were no significant differences in the gene profile for the toll-like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro, microvesicles from patients with asthma impaired the relaxation to bradykinin and contraction to acetylcholine, whereas microparticles from healthy subjects did not. These data suggested that reduction in systemic pro-inflammatory responses and circulating LBP and increased level of norepinephrine in asthma patients persisted even after 2months of the air pollution intervention. These changes were independent of the TLR signaling pathway. Circulating microparticles might be associated with airway smooth muscle dysfunction.

Intentionally induced intestinal barrier dysfunction causes inflammation, affects metabolism, and reduces productivity in lactating Holstein cows

Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 d in milk) were enrolled in 2 experimental periods. Period 1 (5 d) served as the baseline for period 2 (7 d), during which cows received 1 of 2 i.v. treatments twice per day: sterile saline or a gamma-secretase inhibitor (GSI; 1.5 mg/kg of body weight). Gamma-secretase inhibitors reduce intestinal barrier function by inhibiting crypt cell differentiation into absorptive enterocytes. During period 2, control cows receiving sterile saline were pair-fed (PF) to the GSI-treated cows, and all cows were killed at the end of period 2. Administering GSI increased goblet cell area 218, 70, and 28% in jejunum, ileum, and colon, respectively. In the jejunum, GSI-treated cows had increased crypt depth and reduced villus height, villus height-to-crypt depth ratio, cell proliferation, and mucosal surface area. Plasma lipopolysaccharide binding protein increased with time, and tended to be increased 42% in GSI-treated cows relative to PF controls on d 5 to 7. Circulating haptoglobin and serum amyloid A concentrations increased (585- and 4.4-fold, respectively) similarly in both treatments. Administering GSI progressively reduced dry matter intake (66%) and, by design, the pattern and magnitude of decreased nutrient intake was similar in PF controls. A similar progressive decrease (42%) in milk yield occurred in both treatments, but we observed no treatment effects on milk components. Cows treated with GSI tended to have increased plasma insulin (68%) and decreased circulating nonesterified fatty acids (29%) compared with PF cows. For both treatments, plasma glucose decreased with time while β-hydroxybutyrate progressively increased. Liver triglycerides increased 221% from period 1 to sacrifice in both treatments. No differences were detected in liver weight, liver moisture, or body weight change. Intentionally compromising intestinal barrier function caused inflammation, altered metabolism, and markedly reduced feed intake and milk yield. Further, we demonstrated that progressive feed reduction appeared to cause leaky gut and inflammation.

Melatonin from slow-release implants did not influence the gene expression of the lipopolysaccharide receptor complex in the choroid plexus of seasonally anoestrous adult ewes subjected or not to a systemic inflammatory stimulus

This study was designed to determine the effect of melatonin from continuous slow-release implants on (i) the mRNA expression for the lipopolysaccharide (LPS) receptor complex, which includes toll-like receptor 4 (TLR4), myeloid differentiation-2 factor (MD-2) and cluster of differentiation-14 (CD14) in the choroid plexus (CP) and (ii) on the plasma concentration of LPS binding protein (LBP) in ewes subjected or not to a systemic inflammatory stimulus (intravenous injection of LPS). Experiments were conducted in ovariectomized, oestradiol-implanted ewes during seasonal anoestrus (May/June). In experiment 1, the ewes were divided into four groups: sham-implanted and placebo-treated (C/C), melatonin-implanted and placebo-treated (M/C, Melovine 18mg), sham-implanted and LPS-treated for 3h (C/LPS, 400ng/kg of body mass) and melatonin-implanted and LPS-treated for 3h (M/LPS). In experiment 2, the ovariectomized ewes were melatonin-implanted or sham-implanted and treated with LPS for 6h (M/LPS and C/LPS, respectively). Plasma melatonin concentrations reached 4.5±1.5pg/ml in the C/C group, 151.4±56.4pg/ml in the M/C group, 7.8±4.3pg/ml in the C/LPS group and 240.6±93.0pg/ml in the M/LPS group one month after melatonin or sham implantation. Plasma cortisol concentrations remained at basal level throughout the experiment in the control ewes (C/C and M/C), whereas in the LPS-treated ewes, mean cortisol concentrations increased from 13.7±2.4ng/ml to 92.0±10.2ng/ml and from 15.4±5.9ng/ml to 100.0±10.7ng/ml in the C/LPS and M/LPS groups, respectively. The LPS treatment significantly (p≤0.05) increased the mRNA expression for TLR4 and CD14 but had no effect on the MD-2 mRNA expression in the C/LPS and M/LPS groups. Plasma LBP concentration was not affected within 3h of the LPS-treatment (experiment 1) but increased significantly at 4–6h after LPS-treatment in the C/LPS and M/LPS groups (experiment 2). Melatonin from the slow-release implants did not change the mRNA expression of all the examined genes or the plasma LPB concentration. These results allow us to infer that melatonin implantation does not disturb the CP potential to detect the specific microbial components derived from gram-negative bacteria.

No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial

Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation. We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). Excessive amounts of fructose, HFCS, and glucose from SSBs consumed over 8 d did not differentially affect low-grade chronic systemic inflammation in normal-weight to obese adults. This trial was registered at clinicaltrials.gov as NCT01424306.

Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat

The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.

Abstract LB-373: Plasma lipopolysaccharide-binding protein and colorectal cancer risk: A nested case-control study in the Multiethnic Cohort (MEC)

Abstract Lipopolysaccharide (LPS), an endotoxin found on the outer cell wall of gram-negative bacteria, increases inflammatory response signaling, and may play a role in the pathogenesis of several inflammatory-associated diseases, including cancer, diabetes, inflammatory bowel disease, and cardiovascular disease. While LPS is hypothesized to be associated with colorectal carcinogenesis, there are relatively few human studies which have examined this association. Thus, we examined the association between colorectal cancer (CRC) and lipopolysaccharide-binding protein (LBP; a marker of LPS) in 1,760 participants (879 CRC cases and 879 controls) from the Multiethnic Cohort study (MEC). The baseline questionnaire, which was administered between 1993 and 1996, obtained extensive information on demographics, medical and reproductive histories, cigarette smoking, medication use, family history of various cancers, physical activity, and diet using a quantitative food frequency questionnaire. LBP was measured in plasma samples collected between 2001-2005 and incident cancer cases were identified as those occurring after date of plasma collection through 2012 using the Hawaii Tumor Registry (HTR), the Los Angeles County Cancer Surveillance Program (CSP) and the State of California Cancer Registry (CCR), all of which are NCI-funded Surveillance, Epidemiology, and End Results (SEER) registries. Deaths in the cohort were identified by linkage to the state death-certificate files in CA and HI, and with the National Death Index for deaths occurring in other states. Controls were matched to incident cancer cases on age, location, sex, ethnicity, age at phlebotomy, date of specimen collection, time of blood collection, and time since last meal. LBP was grouped into tertiles, with the lowest tertile serving as the reference (mean: 20,797 ng/mL, range: 2,687-27,211 ng/mL). Conditional logistic regression models were used to estimate the multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Covariates were selected a priori and included factors associated with CRC: education, BMI (kg/m2), physical activity, smoking status at time of blood draw, history of intestinal polyps, previous colonoscopy or sigmoidoscopy, diabetes, history of CRC among 1st degree relatives, NSAID use, alcohol consumption, dietary fiber intake, saturated fat intake and hormone replacement therapy use. Compared to individuals whose LBP concentrations were in the lowest tertile, the ORs associated with middle (mean: 32,282 ng/mL, range: 27,211-37,777 ng/mL) and highest (mean: 51,019, range: 37,777-110,390 ng/mL) tertiles were 1.18 (95% CI = 0.85-1.64) and 1.31 (95% CI = 0.92-1.84), respectively, (Ptrend = 0.12). While this study did not find a statistically significant association between LBP and CRC, further studies are needed to understand the interplay between the gut microbiome, LBP, inflammation, and CRC. This work was supported by grants from the National Institutes of Health (grants P01 CA168530, R25 CA094880, and P01 CA33619). Citation Format: Jessica Citronberg, Lynne Wilkens, Loic Le Marchand, Unhee Lim, Meredith Hullar, Emily White, Polly Newcomb, Johanna Lampe. Plasma lipopolysaccharide-binding protein and colorectal cancer risk: A nested case-control study in the Multiethnic Cohort (MEC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-373.

Reliability of plasma lipopolysaccharide-binding protein (LBP) from repeated measures in healthy adults.

Plasma lipopolysaccharide-binding protein (LBP), a measure of internal exposure to bacterial lipopolysaccharide, has been associated with several chronic conditions and may be a marker of chronic inflammation; however, no studies have examined the reliability of this biomarker in a healthy population. We examined the temporal reliability of LBP measured in archived samples from participants in two studies. In Study one, 60 healthy participants had blood drawn at two time points: baseline and follow-up (either three, six, or ninemonths). In Study two, 24 individuals had blood drawn three tofour times over a seven-month period. We measured LBP in archived plasma by ELISA. Test-retest reliability was estimated by calculating the intraclass correlation coefficient (ICC). Plasma LBP concentrations showed moderate reliability in Study one (ICC 0.60, 95% CI 0.43-0.75) and Study two (ICC 0.46, 95% CI 0.26-0.69). Restricting the follow-up period improved reliability. In Study one, the reliability of LBP over a three-month period was 0.68 (95% CI: 0.41-0.87). In Study two, the ICC of samples taken≤sevendays apart was 0.61 (95% CI 0.29-0.86). Plasma LBP concentrations demonstrated moderate test-retest reliability in healthy individuals with reliability improving over a shorter follow-up period.

Molecular Properties of Guar Gum and Pectin Modify Cecal Bile Acids, Microbiota, and Plasma Lipopolysaccharide-Binding Protein in Rats.

Bile acids (BAs) act as signaling molecules in various physiological processes, and are related to colonic microbiota composition as well as to different types of dietary fat and fiber. This study investigated whether guar gum and pectin—two fibers with distinct functional characteristics—affect BA profiles, microbiota composition, and gut metabolites in rats. Low- (LM) or high-methoxylated (HM) pectin, and low-, medium-, or high-molecular-weight (MW) guar gum were administered to rats that were fed either low- or high-fat diets. Cecal BAs, short-chain fatty acids (SCFA) and microbiota composition, and plasma lipopolysaccharide-binding protein (LBP) levels were analyzed, by using novel methodologies based on gas chromatography (BAs and SCFAs) and 16S rRNA gene sequencing on the Illumina MiSeq platform. Strong correlations were observed between cecal BA and SCFA levels, microbiota composition, and portal plasma LBP levels in rats on a high-fat diet. Notably, guar gum consumption with medium-MW increased the cecal amounts of cholic-, chenodeoxycholic-, and ursodeoxycholic acids as well as α-, β-, and ω-muricholic acids to a greater extent than other types of guar gum or the fiber-free control diet. In contrast, the amounts of cecal deoxycholic- and hyodeoxycholic acid were reduced with all types of guar gum independent of chain length. Differences in BA composition between pectin groups were less obvious, but cecal levels of α- and ω-muricholic acids were higher in rats fed LM as compared to HM pectin or the control diet. The inflammatory marker LBP was downregulated in rats fed medium-MW guar gum and HM pectin; these two fibers decreased the cecal abundance of Oscillospira and an unclassified genus in Ruminococcaceae, and increased that of an unclassified family in RF32. These results indicate that the molecular properties of guar gum and pectin are important for their ability to modulate cecal BA formation, gut microbiota composition, and high-fat diet induced inflammation.

The C-terminal Domain Supports a Novel Function for CETPI as a New Plasma Lipopolysaccharide-Binding Protein.

Described by our group a few years ago, the cholesteryl-ester transfer protein isoform (CETPI), exclusively expressed in the small intestine and present in human plasma, lacked a functional identification for a role of physiological relevance. Now, this study introduces CETPI as a new protein with the potential capability to recognise, bind and neutralise lipopolysaccharides (LPS). Peptides derived from the C-terminal domain of CETPI showed that CETPI not only might interact with several LPS serotypes but also might displace LPS bound to the surface of cells. Peptide VSAK, derived from the last 18 residues of CETPI, protected against the cytotoxic effect of LPS on macrophages. At high concentrations, when different cell types were tested in culture, it did not exhibit cytotoxicity by itself and it did prevent the expression of pro-inflammatory cytokines as well as the generation of oxidative stress conditions. In a rabbit model of septic shock, the infusion of peptide VSAK exerted a protective effect against the effects of LPS and reduced the presence of tumor necrosis factor-alpha (TNFα) in plasma. Therefore, CETPI is proposed as a new protein with the capability to advance the possibilities for better understanding and treatment of the dangerous effects of LPS in vivo.

Hepatosplenic schistosomiasis is characterised by high blood markers of translocation, inflammation and fibrosis.

Cirrhosis is the main cause of portal hypertension worldwide but schistosomiasis dominates in much of the tropics. The seroprevalence of Schistosoma mansoni is up to 77% in endemic parts of Zambia. Morbidity is attributed to portal hypertension causing variceal bleeding which can be fatal. Bacterial translocation is associated with portal hypertension in cirrhosis but this is almost unexplored in hepatosplenic schistosomiasis. Liver biopsy is usually used to assess fibrosis although it is invasive and prone to sampling error. We aimed to investigate translocation, fibrosis and inflammatory makers in a case-control study of schistosomiasis at the University Teaching Hospital, Lusaka, Zambia. Patients had oesophageal varices, but were negative for human immunodeficiency virus, hepatitis B and C viruses. Plasma lipopolysaccharide binding protein was used as a marker of translocation while hyaluronan and laminin measured liver fibrosis. Inflammatory markers were measured in blood. Controls were patients with non-specific abdominal pain who had normal endoscopy. Median (interquartile range) lipopolysaccharide binding protein was elevated in patients [44.3 ng/ml (35.7, 57.1)] compared to controls [30.7 ng/ml (30.4, 35.5), P < 0.0001]. Hyaluronan was higher in patients [111.6 ng/ml (39.1, 240.3)] compared to controls [21.0 ng/ml (12.4, 37.6), P < 0.0001] and so was laminin [2.2 μg/ml (1.0, 3.7)] compared to controls [0.9 μg/ml (0.7, 1.2), P = 0.0015]. Inflammatory markers, except C-reactive protein, were elevated in patients. These data suggest that the bacterial translocation contributes to systemic inflammation in hepatosplenic schistosomiasis. Elevated fibrotic markers suggest they may be useful in diagnosing and monitoring periportal fibrosis.

Lipopolysaccharide-binding Protein And Leptin Are Associated With Stress-induced Interleukin-6 Cytokine Expression Ex Vivo In Obesity

Obesity is associated with enhanced inflammation and mental stress, but limited information has addressed the potential additive effect of psychological stress on obesity-associated inflammation. PURPOSE: The purpose of this study was to examine whether obese subjects would elicit a greater host immune response (IL-6 mRNA and cytokine expression) to lipopolysaccharide (LPS) in response to acute mental stress. METHODS: Twenty healthy male subjects (10 obese [age 28.13 ± 2.24 yrs] and 10 normal-weight [24.02 ± 1.50 yrs]) were recruited to participate in a 20 min bout of acute mental stress. Blood samples for LPS-stimulated IL-6 cytokine and mRNA determinations were collected prior to, immediately after, and one hour after stress. RESULTS: We demonstrated that whole blood cells from obese subjects elicited a greater concentration of LPS-induced IL-6 cytokine (p = 0.036) in conjunction with its mRNA expression (p < 0.001) following acute mental stress compared to the cells of the normal-weight subjects. Furthermore, stress-induced IL-6 cytokine response to LPS ex vivo was correlated with the baseline levels of plasma LPS binding protein (LBP) (r = 0.541, p = 0.014) and leptin (r = 0.554, p = 0.010). CONCLUSION: These findings are consistent with the idea that endogenous inflammatory agents (e.g., LBP and leptin), often elevated with obesity, enhance inflammatory responses to psychological stress.

Effects of two whole-grain barley varieties on caecal SCFA, gut microbiota and plasma inflammatory markers in rats consuming low- and high-fat diets

Mixed-linkage β-glucans are fermented by the colon microbiota that give rise to SCFA. Propionic and butyric acids have been found to play an important role in colonic health, as well as they may have extraintestinal metabolic effects. The aim of the present study was to investigate how two whole-grain barley varieties differing in dietary fibre and β-glucan content affected caecal SCFA, gut microbiota and some plasma inflammatory markers in rats consuming low-fat (LF) or high-fat (HF) diets. Barley increased the caecal pool of SCFA in rats fed the LF and HF diets compared with those fed the control diet, and the effect was generally dependent on fibre content, an exception was butyric acid in the LF setting. Furthermore, whole-grain barley reduced plasma lipopolysaccharide-binding protein and monocyte chemoattractant protein-1, increased the caecal abundance of Lactobacillus and decreased the Bacteroides fragilis group, but increased the number of Bifidobacterium only when dietary fat was consumed at a low level. Fat content influenced the effects of barley: rats fed the HF diets had a higher caecal pool of acetic and propionic acids, higher concentrations of amino acids and higher amounts of lipids in the portal plasma and liver than rats fed the LF diets; however, less amounts of butyric acid were generally formed. Interestingly, there was an increase in the caecal abundance of Akkermansia and the caecal pool of succinic acid, and a decrease in the proportion of Bifidobacterium and the Clostridium leptum group. In summary, whole-grain barley decreased HF diet-induced inflammation, which was possibly related to the formation of SCFA and changes in microbiota composition. High β-glucan content in the diet was associated with reduced plasma cholesterol levels.

Low levels of microbial translocation marker LBP are associated with sustained viral response after anti-HCV treatment in HIV-1/HCV co-infected patients.

BackgroundMicrobial translocation (MT) contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) could predict anti-HCV treatment outcome.MethodsPlasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART) treatment) were categorized into sustained viral responders (SVR; n = 21) or non-responders (NR; n = 15) based on treatment outcome. ART starting subjects—were categorized into chronically HCV-infected (CH; n = 24) and mono-infected (HIV; n = 18), based on the HCV infection status. Samples were collected before start (at baseline) of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV) or antiretroviral-therapy and two years after treatment start (at follow up). χ2–test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers.ResultsPlasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06–0.31, p = 0.004) and multivariate analysis (OR: 1.43, 95% CI: 1.1–1.86, p = 0.07).ConclusionIn HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART) may be a more relevant MT marker than LPS and sCD14.

Relationship between postprandial endotoxemia in nonobese postmenopausal women and diabetic nonobese postmenopausal women.

Background:We hypothesised that nonobese postmenopausal women (NoPoW) and diabetic NoPoW (DNoPoW) may be independently associated with postprandial endotoxemia.Materials and Methods:NoPoW and DNoPoW were evaluated for weight, eating habits, physical activity, body circumferences, fasting plasma glucose level, postprandial plasma glucose level, and insulin level. The lipopolysaccharide (LPS) levels and circulating LPS-binding protein (LBP) were determined in serum at fasting, 1 h, 2 h, 3 h, and 4 h after meal intake and their levels were co-related in 80 NoPoW and 80 DNoPoW.Results:Both DNoPoW group and NoPoW group showed a significant increase (P < 0.05) in LPS levels and circulating LBP in plasma after the meal intake, interestingly the increase was higher in the DNoPoW group.Conclusions:Elevated LPS and circulating LBP were associated significantly with DNoPoW group and NoPoW, especially after a meal intake. These findings suggested a role of LPS and LBP in postprandial systemic inflammation in DNoPoW group. Prospective studies are needed to confirm these results.

Acute phase proteins in naturally occurring respiratory disease of feedlot cattle

The aim of this study was to evaluate three acute phase proteins (APP) [haptoglobin (HPT), lipopolysaccharide binding protein (LBP) and transferrin (Tf)] in feedlot cattle with naturally occurring respiratory disease diagnosed by a calf health scoring chart (CHSC). Seventy-seven beef calves were observed for signs of Bovine Respiratory Disease (BRD) during the first 28 days after arrival at the feedlot. Fourteen cases and pen matched controls were selected based on the CHSC. BRD cases were defined as a score of ≥5, while controls were defined as a score ≤4. The mean CHSC score in cases was 6.9 which was significantly greater than the controls 2.8 (P<0.01). Mean plasma LBP and HPT concentrations were significantly greater in cases than controls (P<0.01). Our study results show that measurement of HPT and LBP could be useful in detecting respiratory disease in feedlot conditions. Transferrin concentrations between the two groups were not statistically different.

Association of markers of bacterial translocation with immune activation in decompensated cirrhosis

Bacterial translocation (BT) may cause infections, in particular, spontaneous bacterial peritonitis (SBP). In the absence of overt infection, BT may further stimulate the immune system and contribute to haemodynamic alterations and complications. Bacterial DNA (bDNA) is claimed to be a promising surrogate marker for BT, although its clinical relevance has been questioned. In 38 cirrhotic patients with and without SBP, bDNA in blood and ascites were assessed by 16S rDNA quantitative PCR. Levels of lipopolysaccharide-binding protein in plasma and highly sensitive C-reactive protein, tumour necrosis factor-α, soluble urokinase plasminogen activating receptor, interleukin-6, interleukin 8, interferon-γ inducible protein-10 and vascular endothelial growth factor in plasma and ascites were measured by multiplex cytokine and ELISA assays. In patients without signs of SBP or positive cultures, we found a high frequency of bDNA but low concordance of bDNA between blood and ascites. Markers of inflammation were not significantly different between blood bDNA-positive (22%), ascites bDNA-positive (52%), and bDNA-negative patients. The 16S rDNA PCR failed to show bDNA in two out of six samples with SBP. Sequencing of positive samples did not determine the source of bDNA. bDNA as assessed by this PCR method was largely unrelated to markers of inflammation and does not seem to be of clinical value in the diagnosis of SBP. According to our results, bDNA is not a reliable marker of BT.

Lipopolysaccharide-binding protein and leptin are associated with stress-induced interleukin-6 cytokine expression ex vivo in obesity.

Obesity is associated with enhanced inflammation and mental stress, but limited information has addressed the potential additive effect of psychological stress on obesity-associated inflammation. This study examined whether obese subjects would elicit a greater host immune response (IL-6 mRNA and cytokine) to lipopolysaccharide (LPS) in response to mental stress. Blood samples for LPS-stimulated IL-6 mRNA and cytokine were collected prior to and following mental stress. Results showed that obese subjects elicited a greater LPS-induced IL-6 along with its mRNA expression following mental stress compared to normal-weight subjects. Stress-induced IL-6 cytokine response to LPS was correlated with the baseline levels of plasma LPS binding protein (LBP) and leptin. These findings are consistent with the idea that endogenous inflammatory agents (e.g., LBP and leptin), often elevated with obesity, enhance inflammatory responses to psychological stress.

Circulating pathogen associated molecular pattern – Binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: Implications for cellular Toll-like receptor activity

ObjectiveThe Metabolic Syndrome, (MetS) a global epidemic, is a state of low grade chronic inflammation and confers an increased risk for diabetes and CVD. We have previously reported increased activity of the pathogen recognition receptors, Toll-like receptors (TLRs), TLR2 and TLR4 in MetS. We hypothesized that increased TLR activity in MetS is due in part to increased levels of circulating PAMP–binding proteins, soluble CD14 (sCD14), lipopolysaccharide binding protein (LBP) and the damage associated molecular pattern (DAMP), High Mobility Group Box protein 1 (HMGB-1). MethodsWe measured sCD14, LBP and HMGB-1 in fasting plasma from nascent MetS (n = 37) and healthy control subjects (n = 32) by ELISA. We also investigated the effects of sCD14 and LBP on TLR4 activity in human aortic endothelial cells (HAECs). ResultsFollowing adjustment for body mass index and waist circumference, sCD14, LBP and HMGB-1 levels remained significantly increased in MetS. Also their levels increased with increasing numbers of MetS risk factors. Only sCD14 correlated significantly with monocyte TLR4 protein and activity. None of these soluble biomarkers correlated with TLR2 protein. Both sCD14 and HMGB-1 correlated significantly with HOMA-IR.In LPS primed HAECs, sCD14 compared to LBP, resulted in a greater increase in both TLR4 abundance and inflammatory biomediators (NF-κB, IL-1β, IL-8 and TNF-α). ConclusionThus, we make the novel observation that sCD14 reflects increased monocyte TLR4 protein and activity in nascent MetS and by contributing to increased cellular inflammation could explain, in part, the increased risk for diabetes and CVD.