Serum Leukotriene B4 Research Articles

Volatile Organic Compounds (VOC) and Serum Leukotriene B4 between COPD Patients and COPD with Lung Cancer Patients

Introduction: Chronic obstructive pulmonary disease (COPD) is estimated to become the third leading cause of death worldwide in 2030. COPD can affect the lungs and cause chronic systemic inflammation. Leukotriene B4 (LTB4) is involved in COPD and lung cancer pathogenesis. There has been the development of non-invasive methods for detecting lung disease in the last few decades, such as the examination of volatile organic compounds (VOC). This study aimed to analyze the serum LTB4 and the difference of VOCs in exhaled breath of stable COPD patients and COPD with lung cancer patients. Methods: This case-control study recruited 20 stable COPD patients and 20 patients with COPD and lung cancer. An exhaled breath sample was collected in Tedlar bags and analyzed using an arrayed sensor breath analyzer to check the concentration of VOCs. Meanwhile, a venous blood sample was collected to examine the level of LTB4 using an ELISA kit. Independent t-test and Mann-Whitney test were used to analyze the data. Results: The carbon dioxide (CO2), nitrogen dioxide (NO2), carbon monoxide (CO), benzene (C6H6), and propane (C3H8) levels were significantly different (p <0.05) in COPD-only patients compared to COPD with lung cancer patients. Serum LTB4 increased in both groups. Conclusion: CO2, CO, and C3H8 levels increased, but the NO2 level decreased in COPD patients with lung cancer compared to COPD-only patients. Serum LTB4 increased in COPD with lung cancer patients.

Expression and significance of procalcitonin, leukotriene B4, serum amyloid A, and C-reactive protein in children with different types of pneumonia: An observational study.

This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial group > mycoplasma group > viral group > control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical group > critical group > noncritical group > control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.

Leukotriene B4: A potential mediator and biomarker for cardiac allograft vasculopathy

BackgroundCardiac allograft vasculopathy (CAV) remains the leading cause of long-term graft failure and mortality after heart transplantation. Effective preventive and treatment options are not available to-date, largely because underlying mechanisms remain poorly understood. We studied the potential role of leukotriene B4 (LTB4), an inflammatory lipid mediator, in development of CAV. MethodsWe used an established pre-clinical rat CAV model to study the role of LTB4 in CAV. We performed syngeneic and allogeneic orthotopic aortic transplantation, after which neointimal proliferation was quantified. Animals were then treated with Bestatin, an inhibitor of LTB4 synthesis, or vehicle control for 30 days post-transplant, and evidence of graft CAV was determined by histology. We also measured serial LTB4 levels in a cohort of 28 human heart transplant recipients with CAV, 17 matched transplant controls without CAV, and 20 healthy non-transplant controls. ResultsWe showed that infiltration of the arterial wall with macrophages leads to neointimal thickening and a rise in serum LTB4 levels in our rat model of CAV. Inhibition of LTB4 production with the drug Bestatin prevents development of neointimal hyperplasia, suggesting that Bestatin may be effective therapy for CAV prevention. In a parallel study of heart transplant recipients, we found non-significantly elevated plasma LTB4 levels in patients with CAV, compared to patients without CAV and healthy, non-transplant controls. ConclusionsThis study provides key evidence supporting the role of the inflammatory cytokine LTB4 as an important mediator of CAV development, and provides preliminary data suggesting the clinical benefit of Bestatin for CAV prevention.

Detection of Volatile Organic Compounds (Voc) in COPD Patients and Its Correlation with Serum Leukotriene B4 and Neutrophil

In last few decades, the development of non-invasive method for detecting lung disease has emerged, such as Volatile Organic Compounds (VOC) examination. This study aims to analyze the difference of VOC in exhaled breath of stable COPD and control subjects, also the correlation between VOC with serum Leukotriene B4 and neutrophil.

Association of Inflammatory Indicators and Clinical Signs and Itch in Atopic Dermatitis Patients Treated with Simiao Pill Combined with Halomethasone Cream.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by symptoms such as itchiness, scaling, and erythema. Previous studies have suggested that inflammatory indicators obtained from peripheral blood cell count can serve as markers for atopic dermatitis pruritus and severity. The objective of this study was to investigate whether these indicators are associated with treatment efficacy in AD patients who received a combination of halomethasone cream and Simiao pill (SMP). 131 adult patients diagnosed with AD between January 2020 to August 2022 and treated with topical halometasone ointment combined with oral Simiao pill for a month were recruited and clinical dates of patients were collected. Inflammatory indicators included Eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum leukotriene B4 (LTB4), and thymic stromal lymphopoietin (TSLP) and clinical indexes for assessing eczema area and severity index (EASI) and peak pruritus-numerical rating scale (PP-NRS). Relationship of baseline and changes of these Inflammatory indicators and that of clinical indexes were analyzed. ELR, NLR, LTB4, and TSLP levels have positive association with EASI before treatment, and baseline ELR and LTB4 levels have positive relationship with PP-NRS. ELR, NLR, LTB4, and TSLP showed a significant decrease at week 2 and the low levels were maintained until week 8 after treatment, while no significant changes were observed in levels of MLR and PLR. There was a significant correlation between the decrease of ELR and the decreases of EASI and PP-NRS at weeks 2, 4 and 8 of the treatment. ELR may serve as an effective and convenient indicator in assessing the disease severity and efficacy of SMP therapy for AD.

Modeling of cancer-related body-wide effects identifies LTB4 as a diagnostic biomarker for pancreatic cancer.

SummaryBackgroundCancer elicits a complex adaptive response in an organism. Limited information is available for the body-wide effects induced by cancer. Here, we evaluated multiorgan changes in mouse models of pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions (pancreatic intraepithelial neoplasia, PanIN) to decipher changes that occur during PDAC development.MethodsRNA-sequencing was employed in the brain, colon, stomach, kidney, heart, liver, and lung tissues of mice with PanIN and PDAC. A combination of differential expression analysis and functional-category enrichment was applied for an in-depth understanding of the multiorgan transcriptome. Differentially expressed genes were verified by quantitative real-time polymerase chain reaction. Neutrophil and macrophage infiltration in multiple organs was analyzed by immunohistochemical staining. Leukotriene B4 (LTB4) levels in mouse and human serum samples were determined by enzyme-linked immunosorbent assay.FindingsTranscriptional changes within diverse organs during PanIN and PDAC stages were identified. Using Gene Ontology enrichment analysis, increased neutrophil infiltration was discovered as a central and prominent affected feature, which occurred in the liver, lung, and stomach at the PanIN stage. The brain appeared to be well protected from the sequels of PanIN or PDAC. Importantly, serum LTB4 was able to discriminate PDAC from normal controls, chronic pancreatitis, and intraductal papillary mucinous neoplasms with high performance.InterpretationOur study provides a high-resolution cartographic view of the dynamic multiorgan transcriptomic landscape of mice with PDAC and its precursor lesions. Our findings suggest that LTB4 could serve as a biomarker for the early detection of PDAC.FundingThe complete list of funders can be found in the Acknowledgement section.

Association between the clinical-functional parameters and lipid markers of systemic inflammation in mild asthma complicated with obesity

Aim. To identify the features of the association between the clinical-functional conditions and lipid markers of systemic inflammation (fatty acids, eicosanoids, plasmalogens) of patients with mild asthma and obesity. Materials and methods. Obese (n=80) and nonobese (n = 55) adults with mild, partially controlled asthma aged 28 to 65 years, and nonobese (n = 30) healthy controls had venous blood samples analysed. The ACQ-5 test, spirometry were evaluated. Serum thromboxane B2 (ТХВ2) and leukotriene B4 (LTB4) were analyzed by the enzyme immunoassay method. Fatty acidsas methyl esters (FAMEs) and plasmalogens in the form of dimethyl acetals (DMA) were estimated in blood plasma by gas chromatography-mass spectrometry. Results. In obese patients with asthma, the ACQ-5 test was lower in comparison to nonobese patients. FEV1 decreased by 8 %, FVC by 12% (p &lt; 0.05). A decrease in the level of DMA16: 0 by 17.5 % and DMA18: 0 by 25 % was established in obese asthma patients. The ratio of DMA16:0/FAME 16: 0 declined by 21 %, DMA18:0/FAME18: 0 − by 28 %. A fall in eicosapentaenoic acid (20: 5n3) and a change in the 20:4n6/20:5n3 ratio were found. The level of ТХВ2 and LTB4 was increased regardless of body weight. There was a positive correlation between body mass index and levels of LTB4 (r = 0.46), ТХВ2 (r = 0.49); and a negative correlation between ACQ and ТХВ2 (r = - 0.58). Indicators of lung function (FEV1, FVC, VC) had correlative links with DMA18:0, DMA20:0, eicosapentaenoic acid. Conclusion. We showed the change in the inflammatory fatty acids and eicosanoids synthesis and plasmalogen deficiency in obese-asthma. Established relationships between clinical and functional parameters and lipid markers of systemic inflammation, plasmalogen deficiency in patients with asthma and obesity reveal new pathogenetic mechanisms of the systemic inflammatory process in chronic respiratory diseases.

Effect of halometasone cream combined with Simiao pill on the therapeutic effect and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and the factors influencing its clinical efficacy.

Chronic eczema has the characteristics of a long treatment cycle and repeated attacks, which seriously affects the daily life and work of patients. Topical glucocorticoids are the first-line treatment for chronic eczema. This study aimed to retrospectively analyze the effects of halometasone cream combined with Simiao pill on the efficacy and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and identify the factors influencing its clinical efficacy. We retrospectively collected the medical records of 195 patients with chronic eczema treated in the dermatology department from January 2020 to May 2021, and divided them into two groups according to medication: 98 cases were treated with halometasone cream (control group) and 97 cases were treated with halometasone ointment combined with Simiao pill (observation group). The severity of eczema, quality of life, clinical efficacy, LTB4 and TSLP levels, and safety were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent factors affecting clinical efficacy. After treatment, the Eczema area and severity index (EASI) and Dermatology Life Quality Index (DLQI) scores in the observation group were markedly lower than those of the control group (P<0.05). The total clinical effective rate of the observation group was 88.8%, which was notably higher than that of the control group 70.1% (P=0.001). The concentrations of serum LTB4 and TSLP in the observation group were markedly lower than those in the control group (P<0.05). Logistic regression analysis showed that the treatment regimen, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse were independent factors affecting the curative effect of the patients (P<0.05). Simiao pill combined with halometasone cream can effectively improve chronic eczema and enhance the clinical efficacy of treatment, which may be related to the reduction of serum LTB4 and TSLP levels. The treatment plan, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse are the main factors that affecting the clinical curative effect. Thus, clinical intervention programs should be made according to the above factors to improve the quality of life of patients.

Validity of serum leukotriene B4 as a marker of decompensated liver cirrhosis in chronic HCV patients: leukotriene B4 in decompensated liver cirrhosis

BackgroundLiver cirrhosis is divided into two stages: compensated stage and another advanced stage which includes both decompensated cirrhosis and acute-on-chronic liver failure. The immune system is of major importance in cirrhosis pathophysiology. Sustained bacterial translocation from the intestine to systemic circulation causes a chronic systemic inflammatory syndrome. Inflammatory markers are emerging in the scope of cirrhosis and its complications due to their deleterious effects on disease progression and prognosis. The aim of the study was to assess the value of leukotriene B4 (LTB4) as a marker of decompensated cirrhosis and to evaluate its relation to disease progression and complications.ResultsThe current study was conducted on 80 candidates in the Alexandria Main University Hospital, Tropical Medicine Department; they were categorized into three groups: group I (n = 30) compensated cirrhotic patients, group II (n = 30) decompensated cirrhotic patients, and group III (n = 20) apparently healthy individuals. Serum LTB4 was measured by ELISA. LTB4 showed statistically significant higher values in the decompensated group than the compensated group (p = 0.007) and the control group (p = 0.002). However, there was no statistically significant difference between the compensated group and the controls (p = 0.510). LTB4 correlated positively with the Child-Pugh score (p = 0.003). Moreover, it correlated positively with the MELD-Na score (p = 0.012). There was a significant correlation between the degree of ascites and serum LTB4 (p < 0.001). However, there was no significant correlation between hepatic encephalopathy and LTB4 (P > 0.204).ConclusionSerum LTB4 could be used as a sensitive biomarker of decompensation in cirrhotic patients.

High leukotriene B4 serum levels increase risk of painful diabetic neuropathy among type 2 diabetes mellitus patients

BackgroundPainful diabetic neuropathy is one of the most common complications of type 2 diabetes mellitus, with approximately 30–50% of people will experience diabetic neuropathy. Chronic hyperglycemia will cause an inflammatory process that will trigger an immune response included leukotrienes. Leukotriene B4 is associated with hemoglobin glycation levels. This study aimed to determine high serum leukotriene B4 levels and other factors as a risk factor for painful diabetic neuropathy in type 2 diabetes mellitus patient.ResultsForty-two subjects with 22 cases (median age 56.5 ± 4.9 years) and 20 controls (median age 56.5 ± 5.2 years) group were collected. In bivariate analysis, significant factor for high risk PDN was high leukotriene B4 serum level (OR 5.10; 95% CI 1.34–19.4, p 0.014). Meanwhile, insignificant factors were anti-diabetic drugs (OR 2.139; 0.62–7.37; p = 0.226), and duration of diabetes mellitus (OR 2.282; 0.56–9.25; p = 0.315). Independent risk factor was serum leukotriene B4 levels (OR 5.10; 95% CI 1.336–19.470; p = 0.017).ConclusionsIn this study, high leukotriene B4 serum levels increase the risk of painful diabetic neuropathy among type 2 diabetes mellitus. The leukotriene B4 may consider as a potential biomarker for early detection in high risk for PDN and early treatment.

VALIDITY OF SERUM LEUKOTRIENE B4 AS A PREDICTIVE MARKER OF DECOMPENSATED LIVER CIRRHOSIS IN CHRONIC HCV PATIENTS

Background: Liver cirrhosis is divided into two stages; compensated stage and another advanced stage which includes both decompensated cirrhosis and acute-on-chronic liver failure. The immune system is of major importance in cirrhosis pathophysiology. Sustained bacterial translocation from intestine to systemic circulation causes a chronic systemic inflammatory syndrome. Inflammatory markers are emerging in the scope of cirrhosis and its complications due to their deleterious effects on disease progression and prognosis. The aim of the study was to assess the value of Leukotriene B4 (LTB4) as a predictive marker of decompensated cirrhosis and to evaluate its relation to disease progression and complications.Results: The current study was conducted on 80 candidates in Alexandria main university hospital, Tropical medicine Department, they were categorized into three groups, group I (n=30) compensated cirrhotic patients, group II (n=30) decompensated cirrhotic patients and group III (n=20) apparently healthy individuals. Serum LTB4 was measured by ELISA. LTB4 showed statistically significant higher values in decompensated group than the compensated group (p=0.007) and the control group (p=0.002). However there was no statistically significant difference between the compensated group and the controls (p=0.510). LTB4 correlated positively with Child Pugh score (p=0.003). Moreover, it correlated positively with MELD-Na score (p=0.012). There was significant correlation between degree of ascites and serum LTB4 (p 0.204).Conclusion: Serum LTB4 could be used as a sensitive biomarker of decompensation in cirrhotic patients.

The Relationship between Serum Leukotriene B4 and High-Sensitivity C-Reactive Protein Expression Levels and Adverse Reactions in Patients with Colon Cancer During Perioperative Blood Transfusion

To explore the predictive value of serum high-sensitivity C-reactive protein and leukotriene B4 in perioperative blood transfusion patients with colon cancer in patients with adverse blood transfusion reactions. 168 patients undergoing colon cancer surgery in a hospital from March 2018 to March 2020 were selected as the research objects and checked the levels of high-sensitivity C-reactive protein and leukotriene B4 in the venous blood of all patients. There were 73 cases in the adverse blood transfusion group (experimental group) and 95 cases in the non-transfusion reaction group (control group). The serum levels of high-sensitivity C-reactive protein and leukotriene B4 in the two groups were compared. Based on the analysis of the basic data of the two groups of patients, serum high-sensitivity C-reactive protein and leukotriene B4 are independent risk factors for perioperative adverse reactions in colon cancer patients. The levels of serum high-sensitivity C-reactive protein and leukotriene B4 in the experimental group are higher than those in the normal group and there are differences, both were statistically significant (p<0.05); receiver operating characteristic curve results showed that the area under the curve of high-sensitivity C-reactive protein and leukotriene B4 alone and in combination to predict adverse transfusion reactions were 0.733, 0.819 and 0.877, respectively. The area under the curve of combined factor diagnosis was greater than single diagnosis; serum high-sensitivity C-reactive protein≥14.64 mg/l and leukotriene B4≥18.86 pg/l are risk factors for adverse reactions in patients with colon cancer perioperative blood transfusion. Elevated serum high-sensitivity C-reactive protein and leukotriene B4 in patients with colon cancer during perioperative blood transfusion are risk factors for adverse blood transfusion reactions. High-sensitivity C-reactive protein≥14.64 mg/l and leukotriene B4≥18.86 pg/l suggest that adverse blood transfusion reactions may occur. The combination of the two can increase the incidence of adverse blood transfusion reactions.

Serum leukotriene B4 and hydroxyeicosatetraenoic acid in the prediction of pre-eclampsia

IntroductionPre-eclampsia (PE) affects 2–8% of pregnancies worldwide. Despite identification of numerous possible biomarkers, accurate prediction and early diagnosis of PE remain challenging. We examined the potential of leukotriene B4 (LTB4) and 15-hydroxyeicosatetraenoic acid (15(S)-HETE) as biomarkers of PE by comparing serum levels at three gestational age (GA) groups between normotensive pregnancies and asymptomatic women who subsequently developed preterm or term-PE. MethodsThis is a case-control study drawn from a prospective study of adverse pregnancy outcomes with serum samples collected at 19–24 weeks (n = 48), 30–34 weeks (n = 101) and 35–37 weeks (n = 54) GA. LTB4 and 15(S)-HETE levels were determined by ELISA. Serum level multiples of the median (MoM) were compared between normal and PE-pregnancies. Association between LTB4 and 15(S)-HETE and GA at delivery was investigated with Cox proportional-hazards models. ResultsSerum LTB4 levels were lower in women of East-Asian ethnicity, higher in women with PE history, and increased with GA in normotensive pregnancies, but not in PE. LTB4 was elevated at 19–24 weeks in women who developed preterm-PE. There was a negative association between LTB4 MoM and interval between sampling and delivery with PE at 19–24 weeks only. Serum 15(S)-HETE levels were not influenced by GA at testing and were elevated in women of South-Asian ethnicity. Median 15(S)-HETE levels were unchanged in preterm and term-PE at any GA. DiscussionLTB4 was higher at 19–24 weeks in pregnancies that developed preterm-PE versus unaffected pregnancies, suggesting it is a potentially useful predictive marker of preterm PE in the second trimester.

Promotion of Myofibroblast Differentiation and Tissue Fibrosis by the Leukotriene B4 -Leukotriene B4 Receptor Axis in Systemic Sclerosis.

To investigate the role of the inflammatory lipid mediator leukotriene B4 (LTB4 ) and its receptor, BLT1, in the development and progression of systemic sclerosis (SSc). Serum levels of LTB4 were compared in 64 patients with SSc and 80 healthy controls. Skin and lung tissue sections from patients with SSc and healthy donors were immunostained for leukotriene A4 hydrolase (LTA4 H), the critical enzyme for LTB4 synthesis, and BLT1, in combination with different cell markers. In mouse models of SSc using bleomycin or angiotensin II challenge or immunization with the DNA topoisomerase I, genetic or pharmacologic interruption of the LTB4 -BLT1 axis in mice was carried out to assess its effects on systemic disease features and myofibroblast markers. Immunoblotting was performed to examine the signaling pathway in fibroblasts and endothelial cells following stimulation with LTB4 or with serum from SSc patients. Serum LTB4 levels were 44.93% higher in patients with SSc than in matched healthy controls (mean ± SD 220.3 ± 74.75 pg/ml versus 152.0 ± 68.05 pg/ml; P < 0.0001), and this was associated with the patient subsets of SSc-associated interstitial lung disease and diffuse cutaneous SSc. Levels of LTA4 H and BLT1 were increased in lesional areas of the skin and lungs of SSc patients, and both were abundant in myofibroblasts and endothelial cells. Interruption of the LTB4 -BLT1 axis in mouse models of SSc significantly mitigated dermal and pulmonary fibrosis, with 54.00% and 52.65% fewer α-smooth muscle actin-positive myofibroblasts accumulating in the skin and lungs of mice, respectively, after bleomycin challenge. Immunoblotting of cultures with recombinant LTB4 -stimulated fibroblasts and endothelial cells or with serum from SSc patients showed that fibroblast-myofibroblast and endothelial-mesenchymal transitions were promoted via BLT1, and that this was dependent on activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway but independent of the release of transforming growth factor β (TGFβ) by fibroblasts or endothelial cells. The LTB4 -BLT1 axis may contribute to fibrosis in SSc by directly promoting myofibroblast differentiation via the PI3K/Akt/mTOR pathway, and this appears to operate independently of autocrine secretion of TGFβ.

Serum leukotriene B4 levels, tonsillar hypertrophy and sleep-disordered breathing in childhood

ObjectivesIn children with snoring, increased production of leukotriene B4 (LTB4) may promote tonsillar hypertrophy and sleep-disordered breathing (SDB) or conversely SDB may enhance LTB4 synthesis. We explored whether: i) high LTB4 serum levels predict tonsillar hypertrophy; and ii) SDB severity correlates with LTB4 serum concentration. MethodsNormal-weight children with SDB or controls underwent polysomnography and measurement of LTB4 serum concentration. Tonsillar hypertrophy was the main outcome measure and high LTB4 serum level (>75 t h percentile value in controls) was the primary explanatory variable. Odds ratio (OR) and the corresponding 95% confidence intervals (CI) for tonsillar hypertrophy in children with versus without high LTB4 level were calculated. The control subgroup and subgroups of subjects with increasing SDB severity were compared regarding LTB4 concentration by Kruskal-Wallis test. Spearman's correlation co-efficient was applied to assess the association of LTB4 concentration with SDB severity. ResultsA total of 104 children with SDB and mean obstructive apnea-hypopnea index-AHI of 4.8 ± 5.3 episodes/h (primary snoring: n = 19; mild SDB: n = 49; moderate/severe SDB: n = 36) and 13 controls (no snoring; AHI: 0.4 ± 0.2 episodes/h) were recruited. The four study subgroups were similar regarding LTB4 serum concentration (P = 0.64). High LTB4 (>170.3 pg/mL) was a significant predictor of tonsillar hypertrophy after adjustment for age and gender (OR 3.0 [1.2–7.2]; P = 0.01). There was no association between AHI or desaturation index and LTB4 serum concentration (r = −0.08; P = 0.37 and r = −0.1; P = 0.30, respectively). ConclusionNo association was identified between SDB severity and LTB4 levels, but high LTB4 concentration predicted tonsillar hypertrophy.

Inhibition of 5-lipoxygenase alleviates graft-versus-host disease.

Leukotriene B4 (LTB4), a proinflammatory mediator produced by the enzyme 5-lipoxygenase (5-LO), is associated with the development of many inflammatory diseases. In this study, we evaluated the participation of the 5-LO/LTB4 axis in graft-versus-host disease (GVHD) pathogenesis by transplanting 5-LO-deficient leukocytes and investigated the effect of pharmacologic 5-LO inhibition by zileuton and LTB4 inhibition by CP-105,696. Mice that received allogeneic transplant showed an increase in nuclear 5-LO expression in splenocytes, indicating enzyme activation after GVHD. Mice receiving 5-LO-deficient cell transplant or zileuton treatment had prolonged survival, reduced GVHD clinical scores, reduced intestinal and liver injury, and decreased levels of serum and hepatic LTB4 These results were associated with inhibition of leukocyte recruitment and decreased production of cytokines and chemokines. Treatment with CP-105,696 achieved similar effects. The chimerism or the beneficial graft-versus-leukemia response remained unaffected. Our data provide evidence that the 5-LO/LTB4 axis orchestrates GVHD development and suggest it could be a target for the development of novel therapeutic strategies for GVHD treatment.

Critical Role of LTB4/BLT1 in IL-23-Induced Synovial Inflammation and Osteoclastogenesis via NF-κB.

IL-23 activates the synthesis and production of leukotriene B4 (LTB4) in myeloid cells, which modulate inflammatory arthritis. In this study we investigated the role of LTB4 and its receptor LTB4R1 (BLT1) in synovial inflammation and osteoclast differentiation. Specifically, we used IL-23 in vivo gene transfer to induce arthritis in mice and showed that elevated serum LTB4 and synovial expression of 5-lipoxygenase correlated with increased disease severity by histological evaluation and paw swelling compared with GFP gene transfer controls. To further investigate the effect of the LTB4 pathway in bone loss, we performed osteoclast differentiation assays by stimulating with M-CSF and receptor activator of NF-κB ligand bone marrow cells derived from BLT1+/+ and/or BLT1-/- mice and used quantitative PCR for gene expression analysis in terminally differentiated osteoclasts. Deficiency in BLT1 resulted in the upregulation of osteoclast-related genes and an increase in the formation of giant, multinucleated TRAP+ cells capable of F-actin ring formation. Additionally, BLT1 deficiency showed an increase of phosphorylated NF-κB and phosphorylated IκB levels in osteoclasts. We also performed real-time calcium imaging to study the effect of BLT1 deficiency in receptor activator of NF-κ-B ligand-induced activation of intracellular calcium flux in vitro. Our data show that LTB4 and its receptor BLT1 exacerbate synovial inflammation in vivo and bone resorption in vitro, suggesting that LTB4 and BLT1 could be effectively targeted for the treatment of musculoskeletal diseases.

The anti-inflammatory effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against estradiol-induced nonbacterial inflammation in the rat prostate.

There is no standard treatment of chronic nonbacterial prostatitis in humans. The current study was aimed to investigate the effect of montelukast, an antagonist of cysteinyl leukotriene receptor-1, against estrogen-induced, nonbacterial lateral lobe-specific prostate inflammation in rats. Male Wistar rats were randomized into five groups of six rats, including sham controls (group 1) and castrated rats (group 2), whereas nonbacterial prostatitis (NBP) was induced in groups 3-5 by castration followed by a daily subcutaneous injection of estradiol (0.25mg/kg body weight) for 30days. The rats were left otherwise untreated (group 3) or received a daily oral administration of montelukast (1 and 10mg/kg body weight for groups 4 and 5, respectively) from the 17th day after castration for two consecutive weeks. Compared with sham controls, induction of NBP led to a significant increase in serum leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels, along with a significant upregulation in the transcript level of proinflammatory molecules (nuclear factor kappa beta [NF-κβ] and inducible nitric oxide synthase [iNOS]), chemokines (monocyte chemoattractant protein-1 [MCP-1] and eotaxin), and E-selectin in the lateral prostate. Histological examination revealed intense inflammation in the prostate with leukocyte infiltration and acinar degeneration following estradiol treatment of castrated rats. Montelukast significantly suppressed the increase in serum and prostate proinflammatory mediators/chemokines expression and abolished the histologically inflammatory changes in the lateral prostate. These findings indicate that montelukast inhibits estradiol-induced NBP in a rat model through anti-inflammatory mechanisms, suggesting its future beneficial effect for the treatment of clinical chronic NBP.

Clinical study of serum immunoglobulin E, immunoglobulin G4 and leukotriene B4 levels in children with acute asthma

Objective To evaluate the clinical significance of serum immunoglobulin (Ig)E, IgG4 and leukotriene B4 changes in children with acute asthma. Methods Totally 316 children aged 6 months to 15 years were enrolled and evaluated for the study.Asthma group consisted of 107 patients with acute bronchospasm and histories of recurrent asthma; bronchopneumonia group consisted of 109 patients with bronchopneumonia; and 100 healthy children were assigned as controls.Each group was further divided into 3 subgroups: infants, preschool children and children aged ≥ 7 years.Serum IgE, IgG4 and leukotriene B4 concentrations were determined.The test between 2 groups comparing was performed and compared by the statistical analysis. Results A significant increase in serum IgE levels were observed at all ages in asthma group compared with bronchopneumonia group and control group, respectively, serum IgE levels were also significantly higher in bronchopneumonia group compared with control group (F=60.69, 559.22, P infants > preschool children(F=87.14, P<0.001). Serum IgG4 and leukotriene B4 levels were significantly increased in asthma group and bronchopneumonia group compared with control group, and also in bronchopneumonia group compared with the asthma group (F=97.45, 100.74, P<0.001). However, no significant changes were found among different ages in asthma group. Conclusions The study suggests that infants and schoolchildren with asthma have higher allergic sensitivity.Serum IgG4 should be considered as a protective other than allergic antibody, and enhanced serum leukotriene B4 levels observed in children with acute asthma might be induced by infectious responses. Key words: Asthma; Child; Serum; Immunoglobulin E; Immunoglobulin G4; Leukotriene B4

Interrelationships between ALOX5AP polymorphisms, serum leukotriene B4 level and risk of acute coronary syndrome.

BackgroundWe investigated the relationships between the ALOX5AP gene rs10507391 and rs4769874 polymorphisms, serum levels of leukotriene (LT) B4, and risk of acute coronary syndrome (ACS).MethodsA total of 709 participants, comprising 508 ACS patients (ACS group) and 201 noncoronary artery disease patients with chest pain (control group) were recruited from the Han population of the Changwu region in China. Two polymorphic loci were genotyped using polymerase chain reaction and restriction fragment length polymorphism analysis. Serum LTB4 level was determined by enzyme-linked immunosorbent assay.ResultsSerum LTB4 levels were significantly higher (P<0.001) in the ACS group (median/interquartile range, 470.27/316.32 pg/ml) than in the control group (233.05/226.82 pg/ml). No statistical differences were observed between genotype, allele and haplotype frequencies for the tested loci in either the ACS group or the control group, even after adjustments were made for conventional risk factors by multivariate logistic regression. This suggests there is no association between the ALOX5AP rs10507391 and rs4769874 polymorphisms and ACS risk. Elevated serum LTB4 level was closely linked to ACS risk, and may be independent of traditional risk factors as a risk factor for ACS (P<0.001). There was no significant association between serum LTB4 levels and the two variants in either the ACS group or the control group.ConclusionsRs10507391, rs4769874 and its haplotypes in ALOX5AP are unrelated to ACS risk in the Chinese Han population of Changwu, but elevated serum LTB4 level is strongly associated with ACS risk. Serum LTB4 level is not subject to the influence of either the rs10507391, rs4769874 or the haplotype.