Plasma Lipopolysaccharide-binding Protein Research Articles

Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese.

Although microbiota-derived endotoxaemia has previously been shown to induce metabolic disorders, data from population-based longitudinal studies are scarce. This study therefore investigated the associations between lipopolysaccharide binding protein (LBP) levels and 6 year incident metabolic syndrome (MetS), as well as the potentially modifying effects of obesity status in middle-aged and older Chinese men and women. A total of 2,529 men and women aged 50-70 years from Beijing and Shanghai, China, were followed for 6 years. Those free of MetS at baseline (1,312) were included in the analyses for the risk of developing MetS. Baseline plasma LBP was measured using an ELISA kit. During the 6 year follow-up, 449 (34.2%) participants developed MetS. Baseline LBP was significantly associated with BMI, waist circumference, blood lipid profile and C-reactive protein (CRP) both at baseline and during follow-up (all p < 0.05). The RR for incident MetS comparing extreme quartiles of LBP was 1.28 (95% CI 1.04, 1.58), after multivariate adjustment including BMI and CRP. In stratified analysis, LBP was positively associated with incident MetS only in normal-weight participants (RR, comparing extreme tertiles, 1.59; 95% CI 1.18, 2.15; p(trend)= 0.002), but not in their overweight/obese counterparts (RR, comparing extreme tertiles, 0.99; 95% CI 0.80, 1.22; p(trend) = 0.880). A significant interaction was observed between LBP and obesity status (p(interaction) = 0.013). Our study suggested that elevated plasma LBP was associated with an increased risk of developing MetS among middle-aged and older Chinese, especially in normal-weight individuals.

Influence of the Gut Microbiota on Blood Acute‐Phase Proteins

Little is known about the bovine intestinal microbiota influence on systemic innate immune responses. The objective of the present study was to determine relationships between acute-phase proteins in blood serum of cows [C-reactive protein (CRP), LPS-binding protein (LBP) and haptoglobin (Hp)] and the faecal microbiota. Fifty-two healthy cows (2-8 years old) were investigated. Faecal bacteria were determent characterized by in situ hybridization with 16S/23S rRNA-targeted probes and by conventional culture methods. The population of Gram-negative faecal bacteria (Enterobacteriaceae) was correlated negatively with CRP and positively with LBP in blood plasma, independent of the method used. Similar results were observed with Clostridium perfringens. No correlation was found between the faecal population of intestinal bacteria and Hp levels in blood plasma. This datum indicates that intestinal bacteria, especially Enterobacteriaceae and C. perfringens, may influence the level of CRP and LBP in blood plasma. These findings can be very important for diagnostic evaluations of the intestinal microbiota and provide specific information about its regulation.

Lipopolysaccharide-binding protein (LBP) serum levels in children with OSA and obesity

Obstructive sleep apnea (OSA) has been linked to obesity and the metabolic syndrome (MetS). All these conditions are further tightly linked to inflammation, the origin of the latter still being under debate. In recent years, the gut microbiota and/or gut permeability have emerged as important factors in the vicious cycle of obesity, MetS and inflammation. The gut microbiota, which serves as reservoir for bacterial lipopolysaccharides (LPS), could be altered by OSA and trigger inflammation. Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute-phase protein derived from the liver which has been viewed as a surrogate marker of underlying low level endotoxemia brought about by LPS from the gut. We hypothesized that systemic LBP levels would be higher in obese children and in those with OSA. Consecutive snoring and non-snoring children (mean age: 6.8 ± 1.3 years) were included after they underwent overnight polysomnographic evaluation and a fasting blood sample was drawn the morning after the sleep study. Children were subidivided into 4 sub-groups based on the presence of obesity (BMI z score > 1.65) or OSA (obstructive AHI > 2/hrTST). Plasma LBP levels were assayed using commercial ELISA kits. Of the children studied to date ( n = 56), non-obese controls had lowest levels of LBP, and the presence of obesity without OSA was associated with significant increases in LBP levels ( p < 0.03). Non-obese children with OSA exhibited LBP leves that were similar to those of obese children without OSA ( p < 0.01 vs. non-obese without OSA), with obese children with OSA demonstrating the highest LBP levels of all 4 groups ( p < 0.02 vs. all 3 other groups). Systemic low level endotoxemia and resultant systemic inflammation is present in children who are either obese or suffer from OSA, and is particularly prominent when both conditions are present. We postulate that altered sleep and other factors facilitating obesity such as high fat diet may disrupt the gut microbiome, and lead to increased systemic LPS leaks with resultant inflammation. NIH HL65270.

Lipopolysaccharide-Binding Protein Plasma Levels in Children: Effects of Obstructive Sleep Apnea and Obesity

Obstructive sleep apnea (OSA) has been linked to obesity, inflammation, and metabolic syndrome. The gut microbiota, which serves as reservoir for bacterial lipopolysaccharides (LPS), could be altered by OSA and trigger inflammation. LPS-binding protein (LBP) serves as a surrogate marker of underlying low-grade endotoxemia by LPS from the gut. We hypothesized that systemic LBP levels would be higher in obese children and in those with OSA. Consecutive snoring and nonsnoring children (mean age 6.8 ± 1.3 y) were included after overnight polysomnography, and fasting levels of lipids, insulin glucose, and high-sensitivity C-reactive protein were obtained. Children were subdivided into four subgroups based on the presence of obesity or OSA. Plasma LBP levels were assayed using ELISA. Of 219 participants, nonobese controls had the lowest levels of LBP, and the presence of obesity without OSA was associated with significant LBP increases. Nonobese children with OSA exhibited increased LBP levels, with obese children with OSA demonstrating the highest LBP levels of all four groups. Furthermore, LBP was independently associated with body mass index and with measures of OSA severity as well as with metabolic dysfunction, particularly insulin resistance as indicated by the homeostasis model assessment of insulin resistance. Systemic low-level endotoxemia and resultant systemic inflammation is present in children who are either obese or suffer from OSA and is particularly prominent when both conditions are present. We postulate that disrupted sleep and other factors facilitating obesity such as a high-fat diet may disrupt the gut microbiome and lead to increased systemic LPS levels with resultant inflammation, promoting downstream metabolic dysfunction.

Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin

Hematopoietic cell transplant (HCT) is a life-saving therapy for many malignant and non-malignant bone marrow diseases. Associated morbidities are often due to transplant-related toxicities and infections, exacerbated by regimen-induced immune suppression and systemic incursion of bacterial products. Patients undergoing myeloablative conditioning for HCT become endotoxemic and display blood/plasma changes consistent with lipopolysaccharide (LPS)-induced systemic innate immune activation. Herein, we addressed whether patients scheduled for HCT display differences in recognition/response to LPS ex vivo traceable to specific single nucleotide polymorphisms (SNPs). Two SNPs of LPS binding protein (LBP) were associated with changes in plasma LBP levels, with one LBP SNP also associating with differences in efficiency of extraction and transfer of endotoxin to myeloid differentiation factor-2 (MD-2), a step needed for activation of TLR4. None of the examined SNPs of CD14, bactericidal/permeability-increasing protein (BPI), TLR4 or MD-2 were associated with corresponding protein plasma levels or endotoxin delivery to MD-2, but CD14 and BPI SNPs significantly associated with differences in LPS-induced TNF-α release ex vivo and infection frequency, respectively. These findings suggest that specific LBP, CD14 and BPI SNPs might be contributory assessments in studies where clinical outcome may be affected by host response to endotoxin and bacterial infection.

Induction of CD14 Expression and Differentiation to Monocytes or Mature Macrophages in Promyelocytic Cell Lines: New Approach.

CD14, one of the main differentiation markers on the surface of myeloid lineage cells, acts as a key role in activation of LPS-induced monocytes. LPS (lipopolysaccharide) binds to LPS-binding protein in plasma and are delivered to the cell surface receptor CD14. In this study, Various stimuli [Dimethyl Sulfoxide (DMSO), active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and LPS], either alone or in combination, have been recognized that have an effect on the level of CD14 expression in the human HL-60 and U937 promonocytic cell lines and therefore induce their terminal differentiation into monocytes or mature macrophages. U937 and HL-60 cells were cultured in RPMI 1640 supplemented with 10% FBS. For each cell line, 1Ã106 cells were seeded for 72 hours with DMSO, 14 days with LPS and 18 days with 1, 25-D3 in each well plate; then ELISA method was used to study their responses to the factors by means of anti-CD14. ELISA assay demonstrated that U937 and HL-60 cells were induced by both [1,25(OH)2D3] and DMSO to obtain characteristics of adherent cells and express CD14 protein; moreover, LPS at a low dose increased CD14 expression on surface of this cells. According to the our results, it is speculated that CD14 gene expression may be induced in human U937 and HL-60 cell lines by different factors including 1,25-D3, DMSO and LPS.

Oral administration of LPS and lipoteichoic acid prepartum modulated reactants of innate and humoral immunity in periparturient dairy cows

The study evaluated the effects of repeated oral exposure to LPS and lipoteichoic acid (LTA) on immune responses of dairy cows. Thirty pregnant Holstein cows were randomly assigned to two treatment groups. Cows received orally either 2 ml of 0.85% sterile saline solution (control group), or 2 ml of sterile saline solution containing three doses of LPS from Escherichia coli 0111 : B4 along with a flat dose of LTA from Bacillus subtilis. Blood and saliva samples were collected and analyzed for serum amyloid A (SAA); LPS-binding protein (LBP); anti-LPS plasma IgA, IgG and IgM; TNF-α; and IL-1. Results showed greater concentrations of IgA in the saliva of treated cows compared with the controls (P < 0.01). Treated cows had lower plasma concentrations of anti-LPS IgA, IgG and IgM Abs, and TNF-α than the controls (P < 0.05). There was a tendency for the concentrations of plasma LBP (P = 0.06) and haptoglobin (P = 0.10) to be lesser in the treatment group, although no differences were found in the concentration of plasma SAA and IL-1 (P > 0.10). Overall, the results of this study indicate that repeated oral administration with LPS and LTA stimulates innate and humoral immune responses in periparturient dairy cows.

Defective thymopoiesis and poor peripheral homeostatic replenishment of T-helper cells cause T-cell lymphopenia in cirrhosis

Depletion of circulating CD4(+) T-helper (Th) lymphocytes, especially naive Th cells, is common in cirrhosis. Little is known about the pathogenetic mechanisms involved in Th-cell depletion in cirrhosis. We investigated the mechanisms involved in circulating Th-cell lymphopenia in cirrhosis. Circulating naive and memory Th cells were analyzed by flow cytometry in 60 patients with cirrhosis and 40 sex- and age-matched healthy controls. Thymopoiesis, apoptosis, cell activation, and proliferation were assessed through CD31, annexin-V, HLA-DR and Ki-67 expression, respectively. Lipopolysaccharide (LPS)-binding protein (LBP) and spleen size were measured as indicators of bacterial translocation and splenic pooling, respectively. Compared to controls, patients showed reduced numbers of Th cells involving a greater depletion of the naive than memory Th-cell compartment (2.7- vs. 1.5-fold, respectively). Recent thymic emigrants were diminished (p < 0.01), and each patient had a lower number of CD31(+) naive Th cells than the matched-control. Spontaneous and induced apoptosis (Annexin-V(+)) of Th cells was increased in patients. Activated (HLA-DR(+)) and proliferating (Ki-67(+)) memory Th cells were increased in patients (p < 0.01), and they directly correlated with plasma LBP (p < 0.05) and negatively with naive Th cells (p < 0.01), respectively. Naive Th cells were inversely correlated (p < 0.01) with their frequencies of apoptosis and of activated memory Th cells, LBP, and spleen size. On multivariate analysis, defective thymic generation of naive Th cells, increased memory Th-cell activation, and splenomegaly were independently associated with Th-cell depletion. Th-cell immunodeficiency in cirrhosis is explained by a universal defect in thymopoiesis exacerbated by splenic pooling and activation-driven cell-death induced by bacterial translocation.

Supplemental Naringenin Prevents Intestinal Barrier Defects and Inflammation in Colitic Mice 1-3

Intestinal barrier defects are involved in the pathogenesis of inflammatory bowel disease. The present study investigated the ameliorative effects of naringenin, a citrus polyphenol, on intestinal tight junction (TJ) barrier defects and inflammation in a murine model of colitis. In Expt. 1, using a 2 × 2 fractional design, the mice were administered water or 2% dextran sulfate sodium (DSS) in combination with feeding control or naringenin-containing diets for 9 d (severe disease stage). DSS administration caused severe colon damage and inflammation, as indicated by body weight loss, increased clinical sores, colon shortening, and gene expressions of inflammatory cytokines [interferon-γ, interleukin (IL)-6, macrophage inflammatory protein-2, and IL-17A). DSS administration also impaired TJ barrier integrity in the colon, as indicated by increased colon permeability and plasma LPS-binding protein levels, resulting from the impaired colonic expression of TJ proteins, occludin, junctional adhesion molecule-A, and claudin-3. Supplemental feeding with naringenin totally or partially attenuated these symptoms, suggesting that naringenin ameliorates the DSS-induced colitis at least partially through protection of the TJ barrier. In Expt. 2, analyses were performed at different disease stages (d 3, 6, and 9) to more widely examine the ameliorative role of naringenin on the initiation and development of colitis. DSS administration moderately induced colon shortening at d 3 and 6 and increased the disease activity index (DAI) and inflammatory cytokine (IL-6 and IL-17A) expression without any significant increases in colonic permeability. Feeding naringenin attenuated the increased DAI and colon shortening and tended to suppress the increased cytokine expression. These findings suggest that the presence of an additional mechanism underlying the naringenin-mediated, anticolitic effect along with barrier protection.

Effect of Lipopolysaccharide on Inflammation and Insulin Action in Human Muscle

Accumulating evidence from animal studies suggest that chronic elevation of circulating intestinal-generated lipopolysaccharide (LPS) (i.e., metabolic endotoxemia) could play a role in the pathogenesis of insulin resistance. However, the effect of LPS in human muscle is unclear. Moreover, it is unknown whether blockade/down regulation of toll-like receptor (TLR)4 can prevent the effect of LPS on insulin action and glucose metabolism in human muscle cells. In the present study we compared plasma LPS concentration in insulin resistant [obese non-diabetic and obese type 2 diabetic (T2DM)] subjects versus lean individuals. In addition, we employed a primary human skeletal muscle cell culture system to investigate the effect of LPS on glucose metabolism and whether these effects are mediated via TLR4. Obese non-diabetic and T2DM subjects had significantly elevated plasma LPS and LPS binding protein (LBP) concentrations. Plasma LPS (r = −0.46, P = 0.005) and LBP (r = −0.49, P = 0.005) concentrations negatively correlated with muscle insulin sensitivity (M). In human myotubes, LPS increased JNK phosphorylation and MCP-1 and IL-6 gene expression. This inflammatory response led to reduced insulin-stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport. Both pharmacologic blockade of TLR4 with TAK-242, and TLR4 gene silencing, suppressed the inflammatory response and insulin resistance caused by LPS in human muscle cells. Taken together, these findings suggest that elevations in plasma LPS concentration found in obese and T2DM subjects could play a role in the pathogenesis of insulin resistance and that antagonists of TLR4 may improve insulin action in these individuals.

Combination of biomarkers for the discrimination between bacterial and viral lower respiratory tract infections

To investigate whether additional determinations of plasma lipopolysaccharide binding protein (LBP), procalcitonin (PCT), interleukin-6 (IL-6), IL-18, or soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to C-reactive protein (CRP) improve the discrimination between bacterial and viral lower respiratory tract infections (LRTI). Out of 342 patients visiting the emergency department because of a suspected infection and ≥2 clinical signs of sepsis, 56 patients with proven bacterial (n = 39) or viral (n = 17) LRTI were included. The area under the ROC curves (AUC) of the five possible combinations of CRP with one other biomarker were compared with the AUC of CRP alone. Next, the same analysis was performed in the group of patients with a CRP concentration with <95% specificity for bacterial LRTI. While CRP, PCT, IL-6, sTREM-1, and LBP concentrations were significantly different between patients with bacterial or viral LRTI, the AUC of CRP (0.82, 95% CI 0.70-0.93) did not increase after combination analyses. After exclusion of patients with a CRP >150 mg/l, biomarker panel analyses did not improve diagnostic accuracy of CRP either. Combining CRP with LBP, PCT, IL-6, IL-18, or sTREM-1 does not improve differentiation between patients with a bacterial or viral LRTI compared with CRP alone.

Plasma level of lipopolysaccharide-binding protein is indicative of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

Acute graft-versus-host disease (aGVHD) is the major cause of non-relapse mortality following allogeneic hematopoietic stem cell transplantation. To date, there are no consensus specific plasma biomarkers for aGVHD. We recently identified several candidates differentially expressed in aGVHD patients. Here, we have validated one such candidate: lipopolysaccharide-binding protein (LBP). We detected plasma LBP level by ELISA in 73 patients and performed correlation analysis with the progression and severity of aGVHD. We found that plasma LBP level increased during the period of aGVHD and decreased markedly as aGVHD was resolved. LBP level in patients with moderate aGVHD (25-50 % skin rash area of grade 1 and grade 2) was higher than in patients with no, little (skin rash area <25 % of grade 1), or severe aGVHD (grade 3-4). Higher LBP level indicated higher probability of aGVHD. Multivariate analysis showed that LBP level above 15000 ng/ml was significantly associated with an increased risk of aGVHD (HR 2.43; 95 % CI 1.29-4.58; P = 0.006). If LBP level exceeded 15000 ng/ml at d7 and d14 after HSCT, the subsequent probability of aGVHD increased markedly, especially at the time point of d14. There was no correlation between LBP level and the site of aGVHD. In conclusion, our study demonstrated that an elevated LBP level of >15000 ng/ml may serve as a biomarker for the prediction and monitoring of aGVHD.

A CHARACTERIZATION OF INFLAMMATORY AND STRUCTURAL MARKERS WITHIN THE RUMEN EPITHELIUM DURING GRAIN-INDUCED RUMINAL ACIDOSIS IN LACTATING DAIRY CATTLE

The objective of this study was to characterize the mRNA and protein expression of inflammatory and structural genes in the rumen epithelium during gra in-induced ruminal acidosis in lactating dairy catt le. A total of 16 rumen-fistulated, lactating Holstein da iry cattle (618±35 kg of body weight, 221±32 days i n milk) were used in a randomized complete block design study. All cattle were initially fed a high-forage die t (HF; 88.9% of dry matter) and after a baseline (wk 0) me asurement, half of the cattle were randomly assigne d and transitioned to a high-concentrate diet (HC; 62 .2% of dry matter) which was fed for 3 weeks (weeks 1, 2 and 3). Continuous ruminal pH, ruminal LPS and plasma LPS-binding protein were measured each week followed by a rumen papillae biopsy used for mRNA and protein quantification. After the baseline perio d, ruminal LPS was higher in HC compared to HF cattle (28851±6905 vs. 5771±3042 EU mL -1 ). There was no difference in mRNA expression of inflammatory and structure genes in rumen papillae between HF and HC cattle during all weeks. With regard to protein exp ression, there was an up regulation (p = 0.02) of n uclear factor of activated T-cells cytoplasmic 2 expressio n during weeks 1, 2 and 3; however, all other infla mmatory markers within the rumen epithelium were unchanged by treatment. These results suggest that although g raininduced ruminal acidosis leads to characteristic wh ole-animal inflammatory response, only marginal changes in inflammatory and structural gene and protein expres sion in the rumen epithelium were detected.

STREM‐1 and LBP in Central Venous Catheter–associated Bloodstream Infections in Pediatric Intestinal Failure

Central venous catheter-associated bloodstream infections (CVC-BSIs) are a major cause of morbidity and mortality in the pediatric intestinal failure (IF) population. We assessed plasma lipopolysaccharide-binding protein (LBP) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as biomarkers for CVC-BSI. We hypothesized that sTREM-1 and LBP rise with BSI and decline following treatment, and that baseline LBP is higher in the IF population than in controls. Patients younger than 4 years were recruited from the IF registry at Cincinnati Children's Hospital. LBP and sTREM-1 levels were measured on 22 patients with IF at baseline, 17 patients with IF with BSIs, and 11 healthy controls. Mean sTREM-1 level (pg/mL) and LBP level (μg/mL) rose with CVC-BSI over baseline (115.0 ± 51.2 vs 85.9 ± 27.6, P = 0.011 and 79.8 ± 45.4 vs 20.5 ± 11.3, P < 0.001, respectively) and declined following antibiotic therapy (115.0 ± 51.2 vs 77.9 ± 29.8, P = 0.003 and 79.8 ± 45.4 vs 26.2 ± 10.8, P < 0.001, respectively). Receiver operating characteristic curves showed that neither sTREM-1 nor LBP is sufficient to predict bacteremia versus fever without bacteremia (area under these curves = 0.57 and 0.82, respectively). Baseline LBP was higher in hospitalized patients than in outpatients (27.5 ± 8.7 vs 13.5 ± 9.2, P = 0.002), patients with previous BSIs versus those without (23.5 ± 10.4 vs 10.1 ± 8.3, P = 0.016), and those listed for transplantation versus those not listed (29.6 ± 9.8 vs 16.2 ± 9.5, P = 0.033). sTREM-1 and LBP rise with CVC-BSI in IF and decline after treatment; however, neither distinguishes infection from nonbacteremic febrile episodes. Baseline LBP may be a marker of disease severity in IF.

Origin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression

BackgroundThere is a pressing need to identify novel pathophysiological pathways relevant to depression that can help to reveal targets for the development of new medications. Toll-like receptor 4 (TLR-4) has a regulatory role in the brain's response to stress. Psychological stress may compromise the intestinal barrier, and increased gastrointestinal permeability with translocation of lipopolysaccharide (LPS) from Gram-negative bacteria may play a role in the pathophysiology of major depression.MethodsAdult male Sprague-Dawley rats were subjected to chronic mild stress (CMS) or CMS+intestinal antibiotic decontamination (CMS+ATB) protocols. Levels of components of the TLR-4 signaling pathway, of LPS and of different inflammatory, oxidative/nitrosative and anti-inflammatory mediators were measured by RT-PCR, western blot and/or ELISA in brain prefrontal cortex. Behavioral despair was studied using Porsolt's test.ResultsCMS increased levels of TLR-4 and its co-receptor MD-2 in brain as well as LPS and LPS-binding protein in plasma. In addition, CMS also increased interleukin (IL)-1β, COX-2, PGE2 and lipid peroxidation levels and reduced levels of the anti-inflammatory prostaglandin 15d-PGJ2 in brain tissue. Intestinal decontamination reduced brain levels of the pro-inflammatory parameters and increased 15d-PGJ2, however this did not affect depressive-like behavior induced by CMS.ConclusionsOur results suggest that LPS from bacterial translocation is responsible, at least in part, for the TLR-4 activation found in brain after CMS, which leads to release of inflammatory mediators in the CNS. The use of Gram-negative antibiotics offers a potential therapeutic approach for the adjuvant treatment of depression.

Lipopolysaccharide-Binding Protein for Monitoring of Postoperative Sepsis: Complemental to C-Reactive Protein or Redundant?

IntroductionTo prospectively evaluate the performance of Lipopolysaccharide-Binding Protein (LBP) in prediction of hospital mortality and its correlation to C-reactive Protein (CRP), we studied sixty consecutive, postoperative patients with sepsis admitted to the university hospital intensive care unit.Measurements and MethodsPlasma LBP and CRP were serially measured from day(d)1 (onset of sepsis) to d14 in parallel with clinical data until d28. Predictive value and correlation of LBP and CRP were analyzed by Receiver Operating Characteristic (ROC) curve analysis and Pearson's test, respectively.Main ResultsLBP and CRP showed the highest levels on d2 or d3 after the onset of sepsis with no significant difference between survivors and nonsurvivors. Only at d7, nonsurvivors had significantly (p = .03) higher levels of CRP than survivors. Accordingly, in ROC analysis, concentration of CRP and LBP on d7 poorly discriminated survivors from nonsurvivors (area under curve = .62 and .55, respectively) without significant difference between LBP- and CRP-ROC curves for paired comparison. LBP and CRP plasma levels allocated to quartiles correlated well with each other (r2 = .95; p = .02). Likewise, changes in plasma concentrations of LBP and CRP from one observation to the next showed a marked concordance as both parameters concomitantly increased or decreased in 76% of all cases.ConclusionsDuring the first 14 days of postoperative sepsis, LBP plasma concentrations showed a time course that was very similar to CRP with a high concordance in the pattern of day-to-day changes. Furthermore, like CRP, LBP does not provide a reliable clue for outcome in this setting.

Maternal plasma lipopolysaccharide binding protein (LBP) concentrations in pregnancy complicated by preterm premature rupture of membranes

Objectives To compare maternal plasma LBP concentrations in pregnancies complicated by preterm premature rupture of membranes (pPROM), and PROM at term, with their levels in uncomplicated pregnancy, and to determine whether LBP concentrations are of value in the diagnosis of subclinical intra-amniotic infection (IAI) in the prediction of the length of the pPROM-to-delivery interval, and in the prediction of neonatal congenital infection. Study design Thirty-one patients with pPROM, 35 with PROM at term, 33 healthy women at preterm gestation and 35 healthy women at term were included. In the pPROM group, analysis of maternal plasma LBP concentrations with reference to leukocytosis, C-reactive protein, vaginal fluid culture, neonatal infection and pPROM-to-delivery interval was carried out. Results LBP concentrations in the four studied groups were comparable. Although in 58.1% of pPROM cases at least one laboratory parameter of infection was observed, the only difference concerned the subgroup with CRP above 10 mg/L, in which LBP concentrations were higher. Comparison of LBP concentrations in patients delivered within 24 and 72 h of pPROM and after these times showed no differences, or between patients who gave birth to newborns with and without congenital infection. The predictive values of these measurements were poor. Conclusion The predictive value of maternal LBP determinations in the diagnostics of pPROM cases suspected of IAI is unsatisfactory. LBP measurements performed shortly after pPROM, are not of value either in the prediction of newborn's infection, or in the prognosis of latency period duration.

Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice

This study aimed at determining whether oral administration of a probiotic strain, Lactobacillus casei strain Shirota (LcS), can improve insulin resistance, which is the underlying cause of obesity-associated metabolic abnormalities, in diet-induced obesity (DIO) mice. DIO mice were fed a high-fat diet without or with 0·05% LcS for 4 weeks and then subjected to an insulin tolerance test (ITT) or oral glucose tolerance test (OGTT). Oral administration of LcS not only accelerated the reduction in plasma glucose levels during the ITT, but also reduced the elevation of plasma glucose levels during the OGTT. In addition, plasma levels of lipopolysaccharide-binding protein (LBP), which is a marker of endotoxaemia, were augmented in the murine models of obese DIO, ob/ob, db/db and KK-A(y) and compared to those of lean mice. LcS treatment suppressed the elevation of plasma LBP levels in DIO mice, but did not affect intra-abdominal fat weight. LcS improves insulin resistance and glucose intolerance in DIO mice. The reduction in endotoxaemia, but not intra-abdominal fat, may contribute to the beneficial effects of LcS. This study suggests that LcS has the potential to prevent obesity-associated metabolic abnormalities by improving insulin resistance.

Small Intestinal Bacterial Overgrowth in Nonalcoholic Steatohepatitis: Association with Toll-Like Receptor 4 Expression and Plasma Levels of Interleukin 8

Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS). To compare the prevalence of SIBO and its relationships to LPS receptor levels and systemic cytokines in NASH patients and healthy control subjects. Eighteen NASH patients (eight males) and 16 age-matched and gender-matched healthy volunteers were studied. SIBO was assessed by the lactulose breath hydrogen test (LHBT), plasma lipopolysaccharide binding protein (LBP) levels by ELISA, and expression (as a percentage) of TLR-2 and 4 on CD14-positive cells by flow cytometry. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were measured in plasma. SIBO was more common in NASH patients than control subjects (77.78% vs. 31.25%; P < 0.0001). LBP levels and TLR-2 expression were similar in both groups, TLR-4/MD-2 expression on CD14 positive cells was higher among NASH patients: expression, mean ± SEM, NASH vs. control: 20.95 ± 2.91% vs. 12.73 ± 2.29%, P < 0.05. Among the examined cytokines, only IL-8 levels were significantly higher in patients than control (P = 0.04) and correlated positively with TLR-4 expression (r = 0.5123, P = 0.036). NASH patients have a higher prevalence of small intestinal bacterial overgrowth which is associated with enhanced expression of TLR-4 and release of IL-8. SIBO may have an important role in NASH through interactions with TLR-4 and induction of the pro-inflammatory cytokine, IL-8.

A Marker of Endotoxemia Is Associated With Obesity and Related Metabolic Disorders in Apparently Healthy Chinese

OBJECTIVEElevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese.RESEARCH DESIGN AND METHODSA population-based study including 559 overweight/obese (BMI ≥24.0 kg/m2) and 500 normal-weight (18.0 ≤ BMI <24.0 kg/m2) subjects aged 35–54 years was conducted in Shanghai, China. Fasting plasma glucose, lipid profile, LBP, high-sensitivity C-reactive protein, interleukin-6, high-molecular-weight (HMW) adiponectin, leptin, hepatic enzymes, and body composition were measured. Metabolic syndrome was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans.RESULTSLBP levels were significantly higher in overweight/obese individuals than in normal-weight individuals (geometric mean 27.6 [95% CI 25.2–30.3] vs. 10.0 [9.1–11.1] μg/ml; P < 0.001). After multiple adjustments including BMI, the odds ratios were 3.54 (95% CI 2.05–6.09) and 5.53 (95% CI 2.64–11.59) for metabolic syndrome and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished the significant association of LBP with metabolic syndrome but not that with type 2 diabetes, and controlling for adipokines and hepatic enzymes did not substantially alter the results.CONCLUSIONSElevated circulating LBP was associated with obesity, metabolic syndrome, and type 2 diabetes in apparently healthy Chinese. These findings suggested a role of lipopolysaccharide via initiation of innate immune mechanism(s) in metabolic disorders. Prospective studies are needed to confirm these results.