Value Of Lipopolysaccharide Binding Protein Research Articles

Diagnostic and prognostic value of lipopolysaccharide binding protein and soluble urokinase plasminogen activator receptor in dogs with parvoviral enteritis

Amaç: Bu çalışmada, parvoviral enteritisli köpeklerde lipopolisakkarit bağlayıcı protein (LBP) ve soluble ürokinaz plazminojen aktivatör reseptörünün (suPAR) tanısal ve prognostik değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Bu çalışmanın hayvan materyalini 1-6 ay yaşlar arasında farklı ırk ve cinsiyette kanlı ishal semptomu gösteren hızlı test kiti yardımıyla parvoviral enteritis teşhisi konulan 20 köpek hasta grubunu oluşturdu. Kontrol amacıyla kliniğe getirilen ve yapılan fiziksel muayeneler sonucunda sağlıklı olduğu belirlenen 10 köpek kontrol grubunu oluşturdu. Çalışmadaki köpeklerin tamamından bir defa Vena cephalica antebrachi’den 5 mL jelli serum tüplerine ve 2 mL K2EDTA’lı tüplere kan örnekleri alındı. EDTA’lı kan örneklerinden tam kan sayımı yapıldı. Bulgular: Serum örnekleri ise biyokimyasal ölçümler yapılana kadar -20°C’de muhafaza edildi. Hematoloji bulgularında hasta grupta total lökosit sayısı, eritrosit sayısı, hemoglobin sayısı ve hematokrit yüzdesi kontrol grubuna kıyasla istatistiksel olarak anlamlı düşük bulundu (P<0,05). Hasta grupta kreatinin (P=0,040), üre (P=0,036), total bilirubin (P=0,011), seruloplazmin (P=0,008), haptoglobin (P<0,001) ve LBP (P=0,011) konsantrasyonları kontrol grubuna göre istatistiksel olarak anlamlı yüksek bulurken, albümin (P=0,005) ve suPAR (P=0,012) konsantrasyonları düşük bulunmuştur. Sonuç: Sonuç olarak parvoviral enteritisli köpeklerde seruloplazmin, haptoglobin, LBP ve suPAR diagnostik ve prognostik olarak önemli bulunmuştur.

Analysis of the Value of Serum Biomarker LBP in the Diagnosis of Spinal Tuberculosis.

ObjectiveTo investigate the correlation between the expression of lipopolysaccharide-binding protein (LBP) in peripheral blood of spinal tuberculosis and clinical diagnosis and to evaluate its value as a diagnostic marker of spinal tuberculosis.MethodsIn the experimental group, clinical history data and peripheral blood were collected from 100 patients with spinal tuberculosis who were admitted to the Department of Spine Surgery, General Hospital of Ningxia Medical University from May 2017 to May 2020, and peripheral blood was collected from 30 healthy volunteers in the control group. Screening of differential LBP expression by proteomics and ELISA to verify its expression in peripheral blood of spinal tuberculosis patients. t-test, Spearman analysis, linear regression and ROC curve were used to evaluate the diagnostic value of LBP in peripheral blood for spinal tuberculosis.ResultsThe expression of LBP protein in peripheral blood is significantly higher in patients with spinal tuberculosis than in the normal population; LBP assay values were significantly and positively correlated with CRP and ESR values (P < 0.01); the AUC of LBP in the diagnosis of spinal tuberculosis for pathological examination, bacteriological culture, T-cell spot test for tuberculosis infection (T-SPOT), imaging diagnosis, and acid fast bacillus were, respectively, 0.677 (P < 0.01), 0.707 (P < 0.01), 0.751 (P < 0.01), 0.714 (P < 0.01), and 0.656 (P < 0.05), and there was a correlation between LBP and the diagnostic evaluation of spinal tuberculosis.ConclusionLBP could be a new candidate biomarker for the diagnosis of spinal tuberculosis.

Взаимосвязь между уровнем 25(OH)D3 в крови, количеством противомикробных пептидов в ротовой жидкости и интенсивностью кариеса у молодых лиц

Th e aim of the research. correlation analysis between the DMFT index, the content of the active form of vitamin D – 25(OH)D3 in blood and the level of protective proteins in mixed saliva in young individuals with dental caries. Material and methods. The content of vitamin D metabolite in serum of young individuals with dental caries was evaluated using the chemiluminescent immunoassay method. The concentrations of the antimicrobial peptide – cathelicidin LL-37, alpha-defensin 1-3, secretory immunoglobulin A, lipopolysaccharide binding protein (LBP) in oral fluid were determined using the ELISA method. During dental examination, the analysis of dental caries intensity was conducted through calculating the DMFT index. Statistical processing of the study results was carried out with the “IBM SPSS Statistics Version 25.0” (International Business Machines Corporation, USA) soft ware package. Results. A noticeable inverse relationship between DMFT values, the level of 25(OH)D3 in serum and the values of LBP and sIgA in saliva has been revealed. The content of cathelicidin LL-37, alpha-defensin 1-3, secretory immunoglobulin A and LBP in the oral fl uid of young individuals with dental caries decreases against the background of a low level of serum 25(OH)D3, while noticeable direct correlations between the active form of vitamin D and the value of cathelicidin LL-37, alpha-defensin 1-3 and LBP have been registered. Conclusion. Th e established close relations between the carious process intensity, the volume of 25(OH)D3 in the organism and the immune parameters of saliva confi rm the pathogenetic signifi cance of shift s in the system of oral cavity protection factors.

The clinical significance of lipopolysaccharide binding protein in hepatocellular carcinoma.

Lipopolysaccharide binding protein (LBP) has been reported to be associated with prognosis in colorectal carcinoma and renal cell carcinoma; however, the clinical significance of LBP in human primary hepatocellular carcinoma (HCC) is inconclusive. We aimed to investigate the clinical significance and prognostic value of LBP in human primary HCC. In the present study, 346 patients with HCC who underwent curative resection were retrospectively analyzed. LBP protein expression was evaluated using western blot analysis and immunohistochemistry. LBP scores collected from immunohistochemical analysis were obtained by multiplying staining intensity and the percentage of positive cells. An outcome-based best cutoff-point was calculated by X-tile software. Moreover, Kaplan-Meier curves and Cox regressions were used for prognosis evaluation. LBP was frequently overexpressed in HCC compared with that in peritumor tissues (five pairs by western blot analysis, P=0.0533; 77 pairs by immunohistochemistry, P=0.0171), and LBP expression was positively associated with tumor-node-metastasis stage and tumor differentiation. Patients who had high LBP expression had decreased overall survival and time to recurrence compared with patients with low LBP expression. Furthermore, patients who were both serum α-fetoprotein positive and had high LBP expression had poor prognoses. Univariate and multivariate Cox analyses indicated that this combination was an independent prognostic factor [overall survival: Hazard ratio (HR), 1.458; 95% confidence interval (CI), 1.158–1.837; P=0.001; time to recurrence: HR,1.382; 95% Cl, 1.124–1.700; P=0.002]. In conclusion, LBP is highly expressed in HCC, and high LBP expression combined with serum α-fetoprotein may predict poor outcomes in patients with HCC following curative resection.

Environmental and Clinical Determinants of Plasma-lipopolysaccharide Binding Protein and Association with Non-Alcoholic Fatty Liver Disease in Older Women (P08-022-19)

ObjectivesNonalcoholic fatty liver disease (NAFLD) is an increasingly condition seen in patients with obesity predicting cardiovascular mortality. NAFLD ranges from simple steatosis without significant inflammation(90%), to steatohepatitis (10–30%). Growing evidence suggests that either obesity and gut-flora dysbiosis may activate inflammatory signaling pathways in hepatic cells. Both risk factors may be controlled by dietary components. Manipulated and processed foods consumption would lead to intestinal bacterial overgrowth and/or altered mucosal permeability allowing the bacterial lipopolysaccharides (LPS) to activate TNF-a production in Kupffer cells. OBJECTIVE: Following previous finding that food inadequacy is an environmental risk factor for NAFLD, we presently look at the effects of dietary components on the circulating LPS. MethodsBaseline data of 74 women (35–67 yrs) were analyzed cross-sectional. Analysis included medical, dietary, anthropometry, and plasma biochemistry. Obesity was diagnosed by BMI values and NAFLD by “fatty liver index” ≥60. Plasma immune-nephelometric assay of us-CRP and ELISA of lipopolysaccharide binding protein (LBP) were used as inflammatory markers. LBP values were split into tertiles for comparison with co-variables. SPSS version 19.0 was used to complete ANOVA and evaluated LBP tertiles (T1-T3) at significance level of P = 0.05. ResultsObesity reached 45.9% of the sample and NAFLD, 48.6%. LBP concentrations were significantly higher(T3) in obese and NAFLD women, ingesting high proportion of highly processed diets with high amount of fructose and high sodium/potassium ratio. There was a weak association of higher LBP(T3) with altered us-CRP. Analysis revealed that increased LBP was independently associated with higher intake of fructose and lower polyunsaturated fat, higher glutamic-pyruvic transaminase and higher percentage of body fatness. ConclusionsLBP is associated with body fatness and NAFLD connected to dietary refined food(high fructose and low PUFA), probably impacting gut-flora LPS production and/or translocation to liver, activating TLRs and, from there, spreading systemicaly, bound to liver-born LBP. Funding SourcesACKNOWLEDGEMENTS: Brazilian foundations CNPq and CAPES.

Blood concentrations of lipopolysaccharide-binding protein, high-sensitivity C-reactive protein, tumor necrosis factor-α, and Interleukin-6 in relation to insulin resistance in young adolescents

BackgroundWe assessed the association of insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) with inflammatory molecules, lipopolysaccharide-binding protein (LBP), high sensitivity C-reactive protein (hs-CRP), Tumor necrosis factor-α (TNF-α), and Interleukin-6 (IL-6) in urban young adolescents. MethodsSeventy-six adolescents (36 subjects with HOMA-IR ≥ 2.6 and 40 subjects with HOMA-IR < 2.6) were included in the study. We assessed anthropometric and laboratory measures, such as BMI, blood pressure, insulin sensitivity, liver enzymes, and lipid profiles along with the aforementioned inflammatory biomarkers. The diagnostic accuracy of LBP, hs-CRP, TNF-α, and IL-6 for insulin resistance was evaluated by using the receiver operating characteristic (ROC) curve analysis. ResultsThe mean age of the study subjects was 12.0 [12.0–13.0] y. Circulating LBP plasma concentration and hs-CRP were significantly increased in subjects with HOMA-IR ≥ 2.6 when compared with those with HOMA-IR < 2.6 (P < .0001). There was no difference in TNF-α or IL-6 concentrations between groups. Comparisons based on the area under the ROC curve for LBP, hs-CRP, TNF-α, and IL-6 with regard to insulin resistance (HOMA-IR ≥ 2.6) were 0.8384 (95% CI: 0.7380 to 0.9388), 0.7907 (95% CI: 0.6701 to 0.9113), 0.6207 (95% CI: 0.4770 to 0.7643), and 0.5763 (95% CI: 0.4285 to 0.7241), respectively. ConclusionsAmong LBP, hs-CRP, TNF-α, and IL-6, plasma LBP has the greatest diagnostic accuracy for insulin resistance in young adolescents. Prospective studies are warranted to delineate the value of LBP in the prediction of insulin resistance.

Association of Lipopolysaccharide-Binding Protein With Aging-Related Adiposity Change and Prediabetes Among African Ancestry Men.

Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years). We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ~6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP. LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02-2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067). LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity.

Value of Different Diagnostic Markers in Spontaneous Bacterial Peritonitis in HCV Egyptian Cirrhotic Patients

Background: Spontaneous bacterial peritonitis (SBP) is a life-threatening infection occurring in 8% - 30% of ascitic cirrhotic patients; different laboratory diagnostics play a pivotal role for rapid and effective management of SBP patients. Polymorphonuclear leucocytic (PMNLs) count in Ascitic fluid (AF) is the mainstay for the diagnosis, whereas the diagnostic role of alternative biomarkers is rather controversial. In many studies, serum lipopolysaccharide binding protein (LBP) was elevated and Complement 3 (C3) level was significantly consumed in AF of SBP patients. Objectives: To evaluate the diagnostic value of serum LBP and AF C3 in HCV-cirrhotics with SBP in relation to other well-established serum and AF markers. Patients and Methods: One hundred and twenty patients with HCV-cirrhosis and ascites were enrolled and consented: 50 patients with non-SBP ascites in group A and 70 ascitic patients diagnosed with SBP according to clinical suspicion and PMLs count in AF ≥ 250 cells/mm3 in group B in addition to 15 healthy individuals considered as a control group. Serum LBP, CBC, kidney and liver function tests, CRP, fasting and 2 h PP blood glucose and HCV antibodies were measured. AF samples were sent for C3 level, culture, PMNLs count, LDH, CRP, total proteins and albumin. Results: In patients with SBP, the level of serum LBP was not significantly high (p > 0.05) with best cut off value at 0.4500 and poor AUC (<0.6) with low sensitivity and specificity (53.3% & 57.7%, respectively). AF C3 was significantly reduced in AF (p < 0.001) with best cut off value at 144.2 and almost excellent AUC (0.889) with good sensitivity and specificity (82% & 84%, respectively). AF culture showed significant difference between both patients groups (p < 0.05) but with low sensitivity (33.3%). Serum and AF CRP and AF PMNLs count were of high significance in SBP diagnosis (p < 0.001). Conclusion: Serum LBP level showed low significance while AF C3 was significantly reduced in patients with SBP. AF culture showed significant difference between both groups but with low sensitivity while serum, AF levels of CRP and AF PMNLs count were highly significant, and the latter is still considered the gold standard for SBP diagnosis.

The value of lipopolysaccharide binding protein for diagnosis of late-onset neonatal sepsis in very low birth weight infants.

To assess the accuracy of lipopolysaccharide binding protein (LBP) for diagnosing late-onset neonatal sepsis (LONS) in very low birth weight (VLBW) infants. Observational, prospective study. We assessed the diagnostic performance of LBP in 26 suspected LONS episodes among 54 patients. Proven and probable LONS episodes were recorded according to established criteria. Receiver operating characteristic curve analysis was performed to evaluate LBP's ability to predict LONS. LONS was diagnosed in 17 of 26 episodes. LBP levels were significantly higher in confirmed LONS episodes (P<0.001). The area under the curve of LBP was 0.89. A cut-off of 17.5 μg/mL had a sensitivity of 94.1%, a specificity of 77.8%, a positive predictive value of 88.9% and a negative predictive value of 87.5%. Serum LBP measurement may be useful as an additional tool in the evaluation of suspected LONS in VLBW infants.

P507 DIFFERENCES IN MINIMAL HEPATIC ENCEPHALOPATHY BETWEEN ALCOHOLIC COMPENSATED LIVER CIRRHOSIS AND VIRAL COMPENSATED LIVER CIRRHOSIS

Background and Aims: Intestinal bacterial overgrowth (IBO) and bacterial translocation (BT) induce a marked proinflammatory activity in cirrhotic patients. The aim was to determine the correlation of serum lipopolysaccharide-binding protein (LBP) with severity of cirrhosis, presence of IBO, bacterial DNA in ascitic fluid (AF) and value of LBP in prediction of mortality. Methods: 42 cirrhotic patients were included in the prospective study. IBO was determined by hydrogen breath test (GASTROLYZER, Bedfont, UK). Bacterial DNA in AF were measured using polymerase chain reaction. LBP was measured by immunometric assay (ELISA Human LBP, Netherlands). The survival rate was evaluated during next forty-eight weeks. Statistical analyses were performed using SPSS 13.0. Results: LBP level increased with severity of cirrhosis according to Child–Pugh (p =0.001), it was higher in ascitic patients than in patients without ascites (p < 0.001). Patients with IBO showed greater (p = 0.001) LBP concentration than patients without IBO (15.74±12.56 versus 4.21±2.59mg/mL). Mean serum LBP level was higher in patients with BT (30.13±10.16mg/mL) in comparison with patients without BT (13.56±9.30mg/mL) (p = 0.005). Positive correlation was found between heart rate and LBP level and negative correlation between blood pressure and LBP level (p < 0.001). Using Cox-regression analysis LBP was found to be one of the risk factors of increased mortality during 48 weeks follow-up (p =0.009). Conclusions: Serum LBP elevation shows a significant correlation with severity of cirrhosis, ascites, presence of IBO and hemodynamic disorders. High LBP level is a reliable marker of BT and independent predictor of increased long-term mortality in cirrhotic patients.

Diagnostic value of lipopolysaccharide-binding protein and procalcitonin for sepsis diagnosis in forensic pathology

The aims of this study were twofold. The first was to investigate the diagnostic performance of two biochemical markers, procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP), considering each individually and then combined, for the postmortem diagnosis of sepsis. We also tested the usefulness of pericardial fluid for postmortem LBP determination. Two study groups were formed, a sepsis-related fatalities group of 12 cases and a control group of 30 cases. Postmortem native CT scans, autopsy, histology, neuropathology, and toxicology as well as other postmortem biochemical investigations were performed in all cases. Microbiological investigations were also carried out in the septic group. Postmortem serum PCT and LBP levels differed between the two groups. Both biomarkers, individually considered, allowed septic states to be diagnosed, whereas increases in both postmortem serum PCT and LBP levels were only observed in cases of sepsis. Similarly, normal PCT and LBP values in postmortem serum were identified only in non-septic cases. Pericardial fluid LBP levels do not correlate with the presence of underlying septic states. No relationship was observed between postmortem serum and pericardial fluid LBP levels in either septic or non-septic groups, or between pericardial fluid PCT and LBP levels.

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.

Mid-trimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, TNF-α, and lipopolysaccharide binding protein in normal pregnancies: a prospective evaluation according to parity, gestational age, and fetal gender

To assess mid-trimester amniotic fluid concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender. Cytokine concentrations were measured within a week of amniocentesis during GW 15+0 to 20+6 and correlated with GW at birth, parity, and fetal gender. After exclusion of women with an adverse pregnancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0-5). Ranges for IL-6, IL-8, TNF-α, and LBP were 4.9-2620 pg/mL, 36.2-5843 pg/mL, 8.0-28.2 pg/mL, and 0.06-1.9 μg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-α values did between the 15(th) and 16(th) and the 15(th) and 18(th) weeks of gestation (P<0.05). No significant correlations between cytokine levels and parity or fetal gender were identified. Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-α concentrations. Further analyses are warranted to establish the role of cytokines in predicting adverse pregnancy outcomes.

Lipopolysaccharide Binding Protein Is a Potential Marker for Invasive Bacterial Infections in Children

The aim of this study was to test the hypothesis that elevated lipopolysaccharide binding protein (LBP) serum concentration is a useful marker in the early diagnosis of invasive bacterial infection in children. We measured LBP in serum and cerebrospinal fluid (CSF) of children with proven invasive infection caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Samples were collected from 39 children (aged 2 months to 17 years) with bacterial sepsis (n = 19) or meningitis (n = 20). Bacterial infection was diagnosed when a blood or CSF culture was positive and clinical signs of invasive infection were present. The control group consisted of serum (n = 60) and CSF (n = 19) samples from children with neurologic disease, juvenile idiopathic arthritis or viral infection. In 10 patients with bacterial infection, follow-up samples (24 and 48 hours) were available. LBP values were measured by an immunochemiluminescence analyzer (IMMULITE; DPC Biermann, Bad Nauheim, Germany) and compared with tumor necrosis factor-alpha and interleukin-8 concentrations. The median LBP serum concentrations in patients with bacterial infection were markedly elevated compared with the control groups (45.0 [33.1-55.2] versus 8.3 [6.8-10.1] microg/mL [median and 5-95% confidence interval]; P < 0.0001). Follow-up serum values of LBP were persistently elevated despite adequate antibiotic treatment, whereas tumor necrosis factor-alpha and interleukin-8 concentrations decreased. In contrast, LBP concentrations in the CSF were below the detection limit of 0.5 microg/mL in 67% of patients with bacterial meningitis (median <0.5 microg/mL), whereas tumor necrosis factor-alpha and interleukin-8 levels were highly elevated. LBP serum concentration is elevated in serum of children with invasive bacterial infection and could be a promising diagnostic marker.

Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (SCT) carries a significant risk of severe therapy-associated complications chief among which is acute graft vs.host disease (aGVHD). Animal models indicate that myeloablative chemotherapy compromises the mucosal barrier, thereby allowing translocation of intestinal flora-derived lipopolysaccharides (or endotoxin) that subsequently trigger aGVHD, but there are no comparable data in humans. Our aim was to gain insight into the potential role of endotoxin and endotoxin-induced acute phase proteins in children undergoing SCT. Plasma concentrations of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured in 57 pediatric patients undergoing SCT. In addition plasma endotoxin levels were measured in 25 patients. The previously described rise in CRP was confirmed, and a marked elevation of LBP was observed that peaked at Day 7 (median value, 6.6 microg/ml; P < 0.03 for all pairwise comparisons). CRP and LBP values were significantly correlated (r = 0.77, P < 0.001). A significant but complex relationship was noted between LBP concentrations at Day 0 and severity of subsequent aGVHD (P = 0.02). Of the 25 patients assayed, 11 (44%) had detectable endotoxemia, including 4 who were endotoxin-positive at Day 0. The detection of endotoxemia coupled with marked elevations in LBP at Day 7 raises the possibility that inflammatory responses early after SCT may be driven in part by the entry of lipopolysaccharide into the bloodstream.

Clinical value of lipopolysaccharide-binding protein (LBP) determinations in acute pancreatitis.

Lipopolysaccharide-binding protein (LBP) is a class 1 acute-phase protein that binds and transfers bacterial lipopolysaccharide (LPS). This study investigated the clinical value of measuring LBP for stratifying biochemical severity in acute pancreatitis by using a recently developed fully automated assay technique. We studied 71 patients with acute pancreatitis of whom 41 presented with a necrotizing course. Necrotizing pancreatitis was associated with pancreatic infections in 21 patients and with multiorgan dysfunction syndrome (MODS) in 18 patients. Serum LBP was measured for 14 days by a fully automated immunoassay and CRP was assessed on a daily routine basis. The relative quantitative systemic release of LBP was lower than that observed for CRP; however, the two parameters revealed similar dynamics, with a maximum increase in acute pancreatitis around the fourth day after onset of symptoms. As observed for CRP, LBP was significantly higher in patients who developed complications such as necrosis, pancreatic infections, single or combined MODS than in those who did not. Multiple regression analysis revealed that pulmonary failure and MODS were independent variables associated with enhanced LBP release, while the development of necrosis, pancreatic infections and MODS were the corresponding variables for increased CRP levels. Systemic LBP concentrations are significantly elevated in acute pancreatitis and closely correlate with overall disease severity. However, compared with CRP, LBP does not contribute to an improved severity stratification in acute pancreatitis.

Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome.

The effects of bacterial endotoxin (lipopolysaccharide, LPS) are amplified by lipopolysaccharide binding protein (LBP) and CD14, resulting in cellular activation at very low concentrations of LPS. To investigate the importance of this pathway in acute lung injury, we measured LPS, LBP, and soluble CD14 (sCD14) in the bronchoalveolar lavage fluid (BAL) of 82 patients with acute respiratory distress syndrome (ARDS). LBP and sCD14 increased markedly in BAL of patients with ARDS. sCD14 and LBP each were strongly related to BAL total protein and polymorphonuclear neutrophil (PMN) concentration, whereas LPS concentration was not. Multivariate analyses showed sCD14 to be strongly related to BAL total protein, even after controlling for LPS and LBP concentrations. sCD14 was strongly and independently related to PMN concentration, after controlling for BAL LPS, LBP, and interleukin-8 (IL-8). The BAL LPS concentration was not strongly related to either BAL total protein or BAL PMN. The BAL sCD14 and LBP values were similar in all subgroups of patients with ARDS, and were not related to survival. The serum LBP and sCD14 were elevated in ARDS, but were not related to BAL total protein, LBP, sCD14, PMN, or clinical outcome. Thus, LBP and sCD14 reach high concentrations in the lungs of patients with ARDS, and BAL sCD14 is strongly related to two major indices of lung inflammation: total protein and PMN concentration. CD14-dependent mechanisms may contribute to lung inflammation in ARDS.