Plasma CRP Concentrations Research Articles

The Relationship of Certain Physiological Parameters and VEGF with chronic kidney disease

Chronic kidney disease (CKD) is a major health burden affecting over 10% of the global population. As kidney function deteriorates across progressive CKD stages, systemic inflammation and cytokine activity are upregulated which further drive disease advancement. Vascular endothelial growth factor (VEGF) also becomes increasingly dysregulated with implications for vascular pathology. However, step-wise changes in these pathways correlating with declining renal filtration have not been clearly elucidated : Objective: This study aimed to evaluate the utility of estimated glomerular filtration rate (eGFR) using the MDRD equation for disease staging, and to explore potential non-invasive biomarkers, including inflammatory markers and vascular endothelial growth factor (VEGF) expression, for early prediction of renal dysfunction; Methods: 50 CKD patients categorized into stages 1-4 (n=10 each) and 10 healthy controls were recruited. Serum creatinine was measured enzymatically and eGFR calculated. Plasma TNF-alpha and CRP concentrations were determined by ELISA. Relative VEGF mRNA levels were quantified by RT-qPCR and normalized to GAPDH; Results: Advancing CKD stage showed step-wise increases in serum creatinine (p<0.001) and reductions in mean eGFR (p<0.001). TNF-alpha and CRP also demonstrated significant stage-dependent elevations beginning from early stage 2 disease relative to controls (p<0.01). VEGF expression escalated progressively from ~3 fold in stage 2 to ~129 fold in stage 4 CKD compared to normal individuals (p<0.001); Conclusions: Deteriorating renal function is associated with substantive aggravations in systemic inflammation and VEGF expression. Tracking these biomarkers could enable early detection of underlying pathology prior to onset of severe kidney impairment.

Investigating the Association Between Diet-Induced "Leaky Gut" and the Development of Prediabetes.

Chronic consumption of a high-calorie diet compromises the gut microbiota and the integrity of the intestinal wall, which causes translocation of bacterial lipopolysaccharides (LPS) into the blood. This elicits the secretion of pro-inflammatory cytokines, resulting in inflammation. However, how a high-fat high carbohydrate diet affects intestinal permeability and its possible role in the development of prediabetes have not been investigated. This study investigated the effects of HFHC diet-induced prediabetes on gut microbiota and intestinal permeability in male Sprague Dawley rats. The animals were randomly assigned into the non-prediabetic (NPD) and diet-induced prediabetic (PD) groups (n=6) for 20 weeks. Then, the fecal samples were analyzed to measure the gut microbiota level of Firmicutes, Bacteroidetes, and Proteobacteria in both animal groups. Blood glucose, plasma insulin, serum zonulin, plasma LPS, soluble CD14, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and intestinal fatty-acid binding protein (IFABP) concentrations were measured. The PD group had a reduction in the Firmicutes and an increase in Bacteroidetes and Proteobacteria levels compared to those in the NPD group. Blood glucose, insulin concentration, serum zonulin, and plasma sCD14 concentrations in the PD group increased significantly, while plasma LPS concentrations were similar to the NPD group. Concentrations of plasma TNF-α, IL-6, CRP, and IFABP, an intracellular protein expressed in the intestine, increased in PD compared to the NPD group. the study results cumulatively suggest that chronic consumption of the HFHC diet may be associated with the dysregulation of gut microbiota, leading to increased intestinal permeability.

Investigating the Role of Serum and Plasma IL-6, IL-8, IL-10, TNF-alpha, CRP, and S100B Concentrations in Obstructive Sleep Apnea Diagnosis.

Obstructive sleep apnea (OSA) is a prevalent and underdiagnosed condition associated with cardiovascular diseases, depression, accidents, and stroke. There is an increasing need for alternative diagnostic tools beyond overnight sleep studies that measure the Apnea/Hypopnea Index (AHI). In this single-center, case-control study, we evaluated serum and plasma concentrations of IL-6, IL-8, IL-10, TNF-α, CRP, and S100B in 80 subjects, including 52 OSA patients (27 moderate [15 ≤ AHI ˂ 30], 25 severe [AHI ≥ 30]) and 28 non-OSA controls (AHI 0-5). Participants with OSA showed approximately 2 times higher median concentrations of CRP in plasma, and IL-6 in serum, as well as 1.3 to 1.7 times higher concentrations of TNF-α and IL-8 in plasma compared with the control group. Receiver Operator Characteristic (ROC) curve analysis was performed to evaluate the predictive capabilities of these serum and plasma biomarkers in distinguishing between the OSA and control groups, revealing varying sensitivity and specificity. In summary, in this study, serum and plasma biomarkers CRP, S100B, IL-6, TNF-α, and IL-8 have been shown to be elevated in patients with OSA, correlated positively with disease severity, age, and BMI. These results support the potential role of these biomarkers in diagnosing OSA, supplementing traditional methods such as overnight sleep studies.

Thymoquinone-loaded self-nano-emulsifying drug delivery system against ischemia/reperfusion injury.

In the present study, a self-nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the efficiency of thymoquinone (TQ) in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10days with TQ-loaded SNEDDS. Biochemical analyses, hematoxylin-eosin staining, indirect immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, inflammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ-loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration, and iNOS protein expression. In addition, this formulation exerted an anti-inflammatory effect evidenced by reduced plasma CRP concentration, MPO activity, and gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ-loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS significantly protects rat liver from I/R injury.

Blood Cell Parameters Combined with Inflammatory Markers in the Early Diagnosis of Pulmonary Embolism

Venous thrombosis is a semi-solid formation of blood components that coalesce in the venous system, and the pathological process of its formation is called venous thrombosis. The deep veins of the lower extremities are a common site of prevalence, and the clinical diagnosis of lower extremity deep vein thrombosis can occur independently or as a complication of other diseases. There is a clear link between inflammation and coagulation/anticoagulation, with inflammatory mechanisms upregulating pro-inflammatory factors, downregulating natural anticoagulant substances, and inhibiting fibrinolytic activity; systemic inflammation is a strong pro-thrombotic stimulus; and in vivo, natural anticoagulant substances not only prevent thrombosis, but also deter inflammatory processes. The interconnection between inflammation and coagulation plays an important role in venous thrombosis. In this study, we analyzed the relationship between inflammatory markers CRP and Fg, FVIII:C and FIX:C by measuring plasma CRP concentration, Fg level, FVIII:C and FIX:C levels in patients with DVT diagnosed by ultrasound, and explored the role and mechanism of inflammatory response and coagulation factor abnormalities and the interaction between them in the development of DVT. In this paper, human blood DNA was extracted by phenol-chloroform-isoamyl alcohol extraction, and CRP 1059G/C gene polymorphism was detected by polymerase chain reaction-restriction enzyme segment length polymorphism (PCR-RFLP) nucleotide typing technique, and the genotypes of each subject were distinguished according to the bands seen by gel electrophoresis, and the frequency of each genotype was counted. Plasma CRP concentrations were measured by immunoturbidimetric assay, FVIII:C and FIX:C levels were measured by phase I assay, and plasma Fg levels were measured by coagulation assay in 59 cases (38 males and 21 females, aged 21-82 years, mean 49.67±11.12 years) and 26 controls (17 males and 9 females, aged 32-67 years, mean 50.13±8.96 years). The above indexes were compared between the two groups, and the correlation between CRP and FVIII:C, FIX:C and Fg was analyzed. Polymerase chain reaction-restriction enzyme segment length polymorphism nucleotide typing technique was used to detect the relationship between CRP 1059G/C gene polymorphism and DVT, to further search for risk factors of venous thrombosis, thus providing new ideas for the future prevention and treatment of this disease in clinical practice.

Systemic inflammation mediates the association of heavy metal exposures with liver injury: A study in general Chinese urban adults

Heavy metal exposures have been reported to be associated with increased risk for liver injury. However, the potential mechanisms of the association remain unclear. A repeated-measure study of 9367 observations was conducted to quantify the associations of urinary heavy metals with serum alanine aminotransferase (ALT), a biomarker for liver injury, and assess the mediating role of systemic inflammation in such associations among general Chinese adults. In single-metal models, positive dose-response relationships between urinary vanadium (V), chromium (Cr), copper (Cu), arsenic (As), cadmium (Cd), tungsten (W), and lead (Pb) and serum ALT were observed. In the multiple-metal model containing the seven metals mentioned above, V and Cu remained positively associated with ALT. In longitudinal analyses of 3–6 years, each 1-unit increase in log-transformed levels of V and Cu was associated with an additional rate of annual ALT increase (95% CI) for 1.3% (0.7–1.8%) and 1.3% (0.7–2.0%), respectively. Plasma CRP concentrations were not only positively associated with urinary Cu and Cd, but also positively related with ALT. Furthermore, mediation analyses showed that CRP mediated 4.70% and 7.03% of urinary Cu- and Cd-associated ALT elevations. Our study provides clues for the prevention of heavy metal-induced liver injury.

Fetal Growth Restriction and Subsequent Low Grade Fetal Inflammatory Response Are Associated with Early-Onset Neonatal Sepsis in the Context of Early Preterm Sterile Intrauterine Environment.

There is no information about whether fetal growth restriction (FGR) is an independent risk factor for low-grade fetal inflammatory response (FIR), and which is more valuable for the prediction of early-onset neonatal sepsis (EONS) between low-grade FIR or fetal inflammatory response syndrome (FIRS) in the context of human early preterm sterile intrauterine environment. We examined FIR (umbilical cord plasma (UCP) CRP concentration at birth) according to the presence or absence of FGR (birth weight < 5th percentile for gestational age (GA)) and EONS in 81 singleton preterm births (GA at delivery: 24.5~33.5 weeks) within 72 h after amniocentesis and with sterile intrauterine environment. A sterile intrauterine environment was defined by the presence of both a sterile amniotic fluid (AF) (AF with both negative culture and MMP-8 < 23 ng/mL) and inflammation-free placenta. Median UCP CRP (ng/mL) was higher in cases with FGR than in those without FGR (63.2 vs. 34.5; p = 0.018), and FGR was an independent risk factor for low-grade FIR (UCP CRP ≥ 52.8 ng/mL) (OR 3.003, 95% CI 1.024–8.812, p = 0.045) after correction for confounders. Notably, low-grade FIR (positive likelihood-ratio (LR) and 95% CI, 2.3969 (1.4141–4.0625); negative-LR and 95% CI, 0.4802 (0.2591–0.8902)), but not FIRS (positive-LR and 95% CI, 2.1071 (0.7526–5.8993); negative-LR and 95% CI, 0.8510 (0.6497–1.1145)), was useful for the identification of EONS. In conclusion, FGR is an independent risk factor for low-grade FIR, and low-grade FIR, but not FIRS, has a value for the identification of EONS in the context of the early preterm sterile intrauterine environment.

M2 Monocyte Polarization in Dialyzed Patients Is Associated with Increased Levels of M-CSF and Myeloperoxidase-Associated Oxidative Stress: Preliminary Results

Cardiovascular diseases represent a major issue in terms of morbidity and mortality for dialysis patients. This morbidity is due to the accelerated atherosclerosis observed in these patients. Atherosclerosis is a chronic inflammatory disease characterized by key players such as monocytes, macrophages, or oxidized LDLs. Monocytes-macrophages are classified into subsets of polarized cells, with M1 and M2 macrophages considered, respectively, as pro- and anti-inflammatory. (1) Methods: The monocyte subsets and phenotypes were analyzed by flow cytometry. These data were completed by the quantification of plasma M-CSF, IL-8, CRP, Mox-LDLs, Apo-B, Apo-AI, chloro-tyrosine, and homocitrulline concentrations. The statistical differences and associations between two continuous variables were assessed using the Mann–Whitney U test and Spearman’s correlation coefficient, respectively. (2) Results: Hemodialyzed patients showed a significant increase in their concentrations of CRP, M-CSF, and IL-8 (inflammation biomarkers), as well as chloro-tyrosine and homocitrulline (myeloperoxidase-associated oxidative stress biomarkers). Moreover, we observed a higher percentage of M2 monocytes in the plasma of hemodialysis patients as compared to the controls. (3) Conclusions: Our data suggest that oxidative stress and an inflammatory environment, which is amplified in hemodialysis patients, seems to favor an increase in the concentration of circulating M-CSF, therefore leading to an increase in M2 polarization among circulating monocytes.

1817-P: Elafibranor and Glucagon-Like Peptide-1 Receptor Agonists Synergize to Attenuate Hepatic Inflammation and Fibrosis in a Rodent Model of Obesity, Insulin Resistance, and NASH

Elafibranor and GLP-1 receptor agonists synergize to attenuate hepatic inflammation and fibrosis in a rodent model of obesity, insulin resistance and NASH. Liver steatosis contributes to the development of hepatic insulin resistance and is present in the majority of T2DM patients, who are 50 or older. Therefore, many NAFLD patients with diabetes are currently treated with the antidiabetics, including GLP-1 receptor agonists (GLP-1RA). Elafibranor (ELA), a phase 3 candidate for the treatment of NASH, ameliorates insulin sensitivity and lowers HbA1c in patients with NASH-associated T2DM. The aim of our study was to evaluate the pharmacological benefit of combining GLP-1RA and ELA in the context of NASH-associated insulin resistance. GLP-1RA administration induced body weight loss, reduced insulinemia, HOMA-IR and liver steatosis in obese mice with NASH and insulin resistance, but its action on liver fibrosis was negligible. ELA co-administration allowed for GLP-1RA dose reduction and resolved all NASH features. Food intake was also normalized at reduced GLP-1RA doses. Plasma CRP concentration was reduced by 56% in mice that received the combination treatment. Transcriptomic analyses revealed that the synergism between ELA and GLP-1RA in the liver was limited to the modulation of the inflammatory pathways with no effect on metabolic genes. Since ELA and GLP-1RA also synergize in vitro to reduce TNFa secretion in LPS-activated THP1 macrophages, we postulate that both drugs have a direct action on inflammatory cells in the liver. Further analyses to characterize ELA and GLP-1RA effects on innate and adaptive immune responses will be presented. Conclusion: ELA and GLP-1RA synergize to reduce hepatic inflammation and fibrosis in a model of NASH and obesity. These results suggest a potential therapeutic interest of combining ELA and GLP-1RA for the treatment of T2DM in NASH patients. Disclosure V. Legry: Employee; Self; GENFIT. Stock/Shareholder; Self; GENFIT. E. Descamps: Employee; Self; GENFIT. Employee; Spouse/Partner; GENFIT. Stock/Shareholder; Spouse/Partner; GENFIT. Stock/Shareholder; Self; GENFIT. S. Debaecker: Employee; Self; GENFIT. Stock/Shareholder; Self; GENFIT. N. Stankovic-Valentin: Employee; Self; GENFIT. Stock/Shareholder; Self; GENFIT. P. Parroche: Employee; Self; GENFIT. Stock/Shareholder; Self; GENFIT. N. Degallaix: Employee; Self; GENFIT. Stock/Shareholder; Self; GENFIT. P. Poulain: Employee; Self; GENFIT. Stock/Shareholder; Self; GENFIT. B. Staels: Consultant; Self; Genfit. R. Walczak: Employee; Self; GENFIT. Stock/Shareholder; Self; GENFIT.

Neutrophil gelatinase associated lipocalin a biomarker for bacterial-induced pharyngeal infection-A pilot study.

ObjectivesNeutrophil gelatinase associated lipocalin (NGAL) is secreted from activated neutrophil granulocytes and is considered an acute phase protein. The aim of this pilot study was to determine whether the NGAL concentration in saliva increases in response to a bacterial throat infection and identify pitfalls, which shall be taken into account in a protocol in a larger hypothesis testing study.MethodsSaliva samples for measurement of NGAL concentration where obtained from cases with an acute throat infection (n = 21) and controls (n = 24). Among cases, plasma NGAL, plasma CRP, and whole blood leukocytes, were measured as well.ResultsThere was no significant difference in NGAL saliva concentration between cases and controls overall (p = .31). For both cases and controls, the saliva NGAL concentration decreased significantly after cleansing the mouth with tap water (cases p = .01; controls p = .01). Among cases, a significant positive correlation between saliva NGAL concentrations before mouth cleansing and plasma CRP concentrations (p = .001) was observed. Blood neutrophil granulocyte count presented a nonsignificant positive correlation to saliva NGAL (p = .07).ConclusionWe could not demonstrate a simple association between the salivary NGAL concentration and pharyngeal bacterial infection. Furthermore, the salivary NGAL concentrations were higher among some controls than cases, suggesting that cofounders for example, periodontitis, uneven salivary dilution level, or other exogenous factors affect salivary NGAL content.

Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children.

New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from ex vivo peripheral blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI 0.73–1.0), specificity of 0.66 (95% CI 0.52–0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75–0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively, p < 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47–0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children.

352: Chorionic-vasculitis is associated with more intense fetal and intraamniotic inflammatory-responses in the context of amnionitis

Inflammation or necrosis in amnion is an intermediate or advanced stage of maternal inflammatory response while chorionic vasculitis is an early stage of fetal inflammatory response(FIR) in ascending intrauterine infection(AIUI). Of note, both amnionitis and chorionic vasculitis have been regarded as the same stage III in the conventional process of AIUI. However, we cannot find any information about the comparison in the intensity of FIR and intraamniotic inflammatory response(IAIR) between chorionic vasculitis and amnionitis. The objective of current study is to examine whether the presence of chorionic vasculitis is associated with more intense FIR and IAIR even in the context of amnionitis. FIR and IAIR were examined according to the presence or absence of chorionic vasculitis in 82singleton preterm birth(≤35.5wks) due to either PTL or preterm-PROM in the context of amnionitis. FIR was determined by umbilical cord(UC) plasma CRP concentration at birth, the frequency of fetal inflammatory response syndrome(FIRS; defined as UC plasma CRP at birth≥200ng/ml), and the progression of inflammation in UC(i.e., inflammation-free UC, inflammation restricted to umbilical vein[UV], inflammation in at least one umbilical artery[UA] without extension into Wharton’s jelly, the extension of inflammation into WJ). IAIR was assessed by MMP-8 concentration in 37amniotic fluid(AF) samples obtained within 3days of birth. Chorionic vasculitis was present in 21% of cases with amnionitis. Median UC plasma CRP level at birth(Fig.1[a]) and the frequency of FIRS(Fig.2[a]) were higher, and the progression of inflammation in UC was more advanced(Fig.2[b]) in cases with chorionic vasculitis than in those without chorionic vasculitis. Moreover, cases with chorionic vasculitis had a higher median AF MMP-8 level than those without chorionic vasculitis(Fig.1[b]). Chorionic vasculitis is associated with more intense FIR and IAIR even in the context of amnionitis. This finding suggests that amnionitis and chorionic vasculitis should not be regarded as the same stage in the process of AIUI.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Associations of C-reactive protein and homocysteine concentrations with the impairment of intrinsic capacity domains over a 5-year follow-up among community-dwelling older adults at risk of cognitive decline (MAPT Study).

The World Health Organization (WHO) recently proposed an innovative model of care focusing on functional rather than disease-based perspectives, based on a construct of intrinsic capacity (IC). This study aimed to analyze if low-grade inflammation (LGI) (chronically raised C-reactive protein - CRP) and hyperhomocysteinemia (HHcy) were associated with variation in IC domains (mobility, cognition, psychological and vitality) and in a combined IC Z-score over a 5-year follow-up among non-demented, community-dwelling older adults at risk of cognitive decline. This observational study included 1516 subjects ≥70 years (64.5% female, mean age 75.4 years, SD = 4.5), volunteers from the interventional study Multidomain Alzheimer Preventive Trial (MAPT). Plasma CRP (at baseline, 6 and 12 months) and homocysteine (at baseline) concentrations were measured. LGI was defined as having ≥2 consecutively CRP readings >3 to 10 mg/L between baseline and 12 months, and HHcy was defined as homocysteine >15 μM/L. IC domains were operationalized as follows: Psychological. Depressive symptoms evaluated by the Geriatric Depression Scale (GDS); Mobility. Assessed by the Short Physical Performance Battery (SPPB); Cognitive function. Examined by a Z-score combining four tests; Vitality. Based on hand grip strength. Outcomes were combined into a composite IC Z-score. IC Z-score decreased among groups with no inflammation and LGI after 5 years, but this decrease was more pronounced among the LGI group (unadjusted mean group difference: 0.09, 95%CI: 0.01 to 0.16; p = 0.032). Participants with HHcy also presented IC Z-score decreases over time. Combined conditions provided more pronounced declines, even after adjusting for potential confounders. LGI and HHcy were both related with impairment on the combined IC levels among older adults after a 5-year follow-up. Identifying biomarkers that strongly associate with IC may help to settle strategies aiming to prevent the incidence and slow down the evolution of age-related functional decline and care dependency.

Rosuvastatin, lycopene and omega-3 fatty acids: A potential treatment for systemic inflammation in COPD; a pilot study

Background/AimsChronic Obstructive Pulmonary Disease (COPD) is characterized by airway inflammation, in which contributes to loss of lung function. Systemic inflammation is also a feature of COPD contributing to many associated co-morbidities. Statins, omega-3 fatty acids (docosahexanoic acid, DHA and eicosapentanoic acid, EPA) and lycopene have been shown to decrease systemic inflammation; however their combined effects have not been investigated. This study aims to identify changes in systemic and airway inflammation induced by statins alone or in combination with DHA, EPA and lycopene in COPD. MethodsCOPD patients (n = 11) received rosuvastatin (20 mg/day) for 4 weeks, then a combination of rosuvastatin (20 mg/day), DHA and EPA (1.5 g/day) and lycopene (45 mg/day) for 8 weeks. Blood and sputum were collected and lung function measured by spirometry at baseline, week 4 and 12. Plasma fatty acids were measured using gas chromatography, while plasma carotenoids were analysed using high-performance liquid chromatography. Plasma CRP and IL-6 concentrations were measured using ELISA; and peripheral blood gene expression was measured using the nCounter™ GX Human Inflammation Kit 2. ResultsFollowing the interventions, clinical characteristics and plasma IL-6 and CRP were unchanged. Sputum neutrophil proportion and absolute count was increased and macrophage proportion decreased by rosuvastatin (P = 0.020 and P = 0.015; respectively). Rosuvastatin increased LTB4R and decreased CXCL10 and AGER gene expression in white blood cells. The addition of lycopene and omega-3 fatty acids decreased LTB4R and increased CXCL10 to basal levels, whilst combined use of interventions increased ALOX15 blood gene expression. ConclusionThis study shows that rosuvastatin, omega-3 fatty acids and lycopene have some anti-inflammatory effects systemically, but rosuvastatin may increase airway neutrophils, which would be undesirable in COPD patients, warranting further investigation.

Elevations in C-reactive protein and endothelin-1 system activity in humans

AimsC-reactive protein (CRP) is an inflammatory cytokine that has been shown to be an independent predictor of future atherothrombotic events. Hyperactivity of endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by the endothelium, is linked with cardiovascular disease development and progression. ET-1 is sensitive to inflammatory stimuli, though the influence of CRP on ET-1 system activity is unknown. We tested the hypothesis that ET-1-mediated vasoconstrictor tone is enhanced in adults with elevated plasma CRP concentrations. Materials and methodsSixty non-obese adults (43–70years) were studied: 20 with hsCRP<1.0mg/L (low CRP; 0.5±0.1mg/L); 20 with hsCRP 1.0–3.0mg/L (moderate CRP; 2.0±0.1mg/L); and 20 with hsCRP>3.0mg/L (high CRP; 6.3±0.5mg/L). Forearm blood flow (FBF; plethysmography) was determined in response to intra-arterial infusions of ET-1 (5pmol/min for 20min) and selective ETA receptor blockade (BQ-123, 100nmol/min for 60min). Key findingsIn response to ET-1, FBF decreased ~10% in the low (−10.0±2.3%), moderate (−10.7±4.0%), and high (−6.6±5.2%) CRP groups, with no significant differences between groups. Additionally, all groups demonstrated a marginal, though significant (~10%), vasodilator response to BQ-123; however, there were no differences in the FBF response to BQ-123 across CRP groups. There were no significant correlations between plasma CRP concentrations and peak FBF response to either ET-1 or BQ-123. SignificanceThese results indicate that ET-1 system activity is not influenced by elevations in CRP. Enhanced ET-1 system activity may not be involved in the increased cardiovascular disease risk associated with elevations in plasma CRP concentrations.

Dietary Omega-3 Fatty Acid Supplementation Reduces Inflammation in Obese Pregnant Women: A Randomized Double-Blind Controlled Clinical Trial.

ObjectiveLong-chain omega 3 fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) exert potent anti-inflammatory properties in humans. This study characterized the effects of omega-3 ω-3 fatty acids supplements (ω-3 FA) on the inflammatory status in the placenta and adipose tissue of overweight/obese pregnant women.Study DesignA randomized, double-masked controlled trial was conducted in overweight/obese pregnant women that were randomly assigned to receive DHA plus EPA (2g/day) or the equivalent of a placebo twice a day from week 10–16 to term. Inflammatory pathways were characterized in: 1) adipose tissue and placenta of treated vs. untreated women; and 2) adipose and trophoblast cells cultured with long chain FAs.ResultsThe sum of plasma DHA and EPA increased by 5.8 fold and ω-3 FA/ ω-6 FA ratio was 1.5 in treated vs. untreated women (p< 0.005). Plasma CRP concentrations were reduced (p<0.001). The adipose tissue and placenta of treated women exhibited a significant decrease in TLR4 adipose and placental expression as well as IL6, IL8, and TNFα In vitro, EPA and DHA suppressed the activation of TLR4, IL6, IL8 induced by palmitate in culture of adipose and trophoblast cells.ConclusionSupplementation of overweight/obese pregnant women with dietary ω-3 FAs for >25 weeks reduced inflammation in maternal adipose and the placental tissue. TLR4 appears as a central target of the anti-inflammatory effects at the cellular level.Trial RegistrationClinicalTrials.gov NCT00957476

Minimal Impact of Nutrition Education and Fruit and Vegetable Consumption on Biomarkers of Inflammation and Oxidative Stress

Aims: To determine the effectiveness of a community-based fruit and vegetable education program and provision of fruits and vegetables on consumption of fruits, vegetables, antioxidants, and changes in biomarkers of inflammation and oxidative stress among overweight and obese adults. Study Design: Randomized controlled design. Place and Duration of Study: North Dakota State University, Fargo, North Dakota; 14 weeks. Methodology: Forty-seven adults (31 women; 45.9 ± 11.8 y; body mass index 32.7 kg/m 2 ) were randomly assigned to one of three intervention groups. The control group received no intervention, the education group attended weekly nutrition education lessons, the fruit and vegetable group attended weekly nutrition education lessons and received one serving of fruits and two servings of vegetables per day for 10 weeks. Fasting blood was drawn and consumption of fruits, vegetables, Original Research Article Wagner et al.; EJNFS, 5(3): 179-189, 2015; Article no.EJNFS.2015.017 180 and antioxidants was assessed using three-day food records. Results: Increased consumption of fruit from preto post-test was indicated among fruit and vegetable group participants, P = .01, and among education group participants, although this difference was not significant, P = .11. In contrast, a significant decrease in fruit servings consumed from preto post-test for control group participants was observed, P = .02. Vegetable consumption was the same for control group participants, decreased by 0.3 serving among education group participants, and increased by 0.4 serving among fruit and vegetable group participants. No significant differences in plasma TNF-α, TBARS, or CRP concentrations from preto post-test were indicated among the three groups, although the largest decrease was observed among fruit and vegetable group participants, P = .07. Conclusion: Changes in fruit and vegetable consumption among participants were minimally associated with improvements in inflammation and oxidative stress biomarkers. Adequate and varied fruit and vegetable consumption is recommended to aid in the prevention and regulation of inflammation and oxidative stress.

Factors affecting immunogenicity of BCG in infants, a study in Malawi, The Gambia and the UK

BackgroundBCG immunogenicity in infants differs between populations and these differences have been attributed to various factors. In this study, the influence of geographical location, season of birth, timing of vaccination, micronutrient status (zinc) and inflammatory status (C-reactive protein, CRP) were assessed.MethodsImmunogenicity was assessed by cytokine signature in culture supernatants from diluted whole blood samples stimulated with M. tuberculosis PPD, using a multiplex bead assay. Results were correlated with the plasma zinc and CRP concentrations at the time of sampling, and with interview and household data. BCG vaccinated infants were recruited in Malawi, The Gambia and the UK.ResultsIn Malawi, infants vaccinated within the first week after birth showed lower production of most cytokines measured than those vaccinated later. The number of cytokines showing significant differences between Malawian and Gambian infants decreased after adjusting for season of birth. In Malawi, a proportion of infants had zinc deficiency and elevated plasma CRP (>10 mg/L), but neither zinc deficiency nor high CRP was associated with production of any of the cytokines measured.ConclusionsThe cytokine/chemokine signatures observed in response to M. tuberculosis PPD in infants at 3 months post BCG vaccination were affected by geographical location, season of birth, and timing of vaccination but not associated with the concentration of plasma zinc or inflammatory status. These factors should be considered in future trials of new TB vaccines.

The Relationship between Inflammatory Biomarkers and Telomere Length in an Occupational Prospective Cohort Study

BackgroundChronic inflammation from recurring trauma is an underlying pathophysiological basis of numerous diseases. Furthermore, it may result in cell death, scarring, fibrosis, and loss of tissue function. In states of inflammation, subsequent increases in oxidative stress and cellular division may lead to the accelerated erosion of telomeres, crucial genomic structures which protect chromosomes from decay. However, the association between plasma inflammatory marker concentrations and telomere length has been inconsistent in previous studies.ObjectiveThe purpose of this study was to determine the longitudinal association between telomere length and plasma inflammatory biomarker concentrations including: CRP, SAA, sICAM-1, sVCAM-1, VEGF, TNF-α, IL-1β, IL-2, IL-6, IL-8, and IL-10.MethodsThe longitudinal study population consisted of 87 subjects. The follow-up period was approximately 2 years. Plasma inflammatory biomarker concentrations were assessed using highly sensitive electrochemiluminescent assays. Leukocyte relative telomere length was assessed using Real-Time qPCR. Linear mixed effects regression models were used to analyze the association between repeated-measurements of relative telomere length as the outcome and each inflammatory biomarker concentration as continuous exposures separately. The analyses controlled for major potential confounders and white blood cell differentials.ResultsAt any follow-up time, each incremental ng/mL increase in plasma CRP concentration was associated with a decrease in telomere length of −2.6×10−2 (95%CI: −4.3×10−2, −8.2×10−3, p = 0.004) units. Similarly, the estimate for the negative linear association between SAA and telomere length was −2.6×10−2 (95%CI:−4.5×10−2, −6.1×10−3, p = 0.011). No statistically significant associations were observed between telomere length and plasma concentrations of pro-inflammatory interleukins, TNF-α, and VEGF.ConclusionsFindings from this study suggest that increased systemic inflammation, consistent with vascular injury, is associated with decreased leukocyte telomere length.

C-reactive protein 1059G/C gene polymorphism, C-reactive protein levels and acute myocardial infarction

High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker, predicting the occurrence of acute myocardial infarction (AMI). Genetic predisposition to high baseline CRP might account for a high risk of heart diseases. Our study aimed at investigating an association of CRP 1059G/C gene polymorphism with plasma CRP levels and AMI in Egyptian patients. Genotypes of 150 patients with AMI and 150 healthy sex and age-matched controls were analyzed using PCR-restriction fragment length polymorphism methods. hs-CRP concentrations were assessed. There was no significant association between CRP 1095G/C polymorphism and AMI. However, individuals with GG genotype had significantly higher plasma CRP concentration than those with GC and CC genotypes, in both controls (3.82 ± 1.03 vs. 2.34 ± 0.7; P = 0.001) and patients with AMI (8.39 ± 2.6 vs. 6.67 ± 2.4; P = 0.005). Our results revealed that CRP 1059G/C gene variation influences plasma CRP levels. Conversely, this polymorphism was not associated with the risk for AMI.