High-fat meal increases peripheral blood mononuclear cell pro-inflammatory cytokine expression in African-American women.

African-American (AA) women have elevated predominance of inflammatory diseases concurrent with local inflammation resulting in compromised metabolic function. The purpose of the study was 2-fold: 1) to examine the gene and protein expression of pro- and anti-inflammatory cytokine secretion by peripheral blood mononuclear cells (PBMC) obtained from AA and Caucasian-American (CA) women in response to an acute high-fat meal; and 2) to explore the influence of race (AA vs. CA) on PBMC reactivity. Ten AA and 11 CA women consumed a high-fat meal with baseline and 4 h postprandial venous blood draws. PBMCs were incubated for 3 h then messenger RNA expression and supernatant protein concentration was used to examine inflammatory profiles. All women had a postprandial increase in interleukin (IL)-8 gene expression, IL-8 protein concentration, and tumor necrosis factor alpha (TNF-α) protein concentration (P < 0.05). AA women had a postprandial increase in IL-6, IL-8, and TNF-α protein concentration (P < 0.05). AA women had higher postprandial IL-1ß protein concentration and IL-8 gene expression compared with CA women (P < 0.05). Our data uncovers the specific impact of race and time on pro-inflammatory PBMC (IL-1ß, IL-6, IL-8, and TNF-α) expression profiles in response to an acute high-fat meal challenge. Novelty: African Americans have higher predominance of inflammatory disease. We explored the potential race impact on peripheral blood mononuclear cell reactivity in response to a meal. A pro-inflammatory response to an acute high-fat meal with race impact was observed possibly contributing to health disparities impacting African-American women.

Assessment of Interleukin-8 in Bronchial Asthma in Iraq.

It has been approved that neutrophils are responsible for many inflammatory lung diseases, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma. It is well documented that the CXC chemokine interleukin-8 (IL-8) plays a key role as a potent neutrophil recruiting and activating factor. Asthma is one of the most common major non-contagious diseases and has a substantial impact on the patient's quality of life. The current evidence suggests that asthma is a complex multifactorial disorder, and its etiology is increasingly attributed to interactions between genetic susceptibility, host factors, and environmental exposures. IL-8 plays an important role in respiratory diseases and is a known regulator of pulmonary inflammation and immunity, induced phagocytosis, and promoted angiogenesis. This study aimed to investigate the IL-8 gene expression in blood samples of bronchial asthma patients. Therefore, the blood samples were taken from two groups of participants, including the group of patients with asthma (n=100) in the age range of20-61years and the group of healthy individuals (n=50).The obtained results indicated that the expression of IL-8 mRNA in the group of asthma patients was three times higher than that in the group of healthy individuals. Therefore, it is suggested that the antagonism of IL-8 could be a potent therapeutic strategy in the treatment of asthma.

Obesity Risk Assessment Tool among 3-5 Year Olds: Validation with Biomarkers of Low-Grade Chronic Inflammation.

Background: Many families with young children practice nutrition, parenting, and lifestyle behaviors that set their children on trajectories for unhealthful weight gain. Potential adverse health effects of excessive body fat can result in the secretion of proinflammatory molecules and increased risk of inflammation and metabolic diseases. A pediatric obesity risk assessment tool named Healthy Kids (HK), demonstrated validity in a longitudinal study with child's measured BMI and 36-hour diet, screen, sleep, and activity logs. Our objective was to provide additional evidence of validity with low-income families with literacy issues using an inflammation index composed of four proinflammatory biomarkers. Methods: Parent/child pairs (n = 104) from Head Start and Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provided HK, blood samples, and measured heights/weights. Select child inflammatory markers were discretized into two groups of HK scores. Data were analyzed with a mixed model adjusted for children's age and BMI. Results: A significant HK-time interaction effect was shown for the child inflammation index with two data collection points 1 year apart (pdid = 0.039). This index increased over 12 months in children with less healthful behaviors (p = 0.007), but not in children with more healthful profiles (p = 0.58). Conclusions: Children with less healthful HK scores had an elevated inflammation index indicating a low-grade chronic systemic inflammatory state. Taken together with our previously published findings, the HK tool has potential as a rapid and easy-to-administer assessment of the family environment and the child's obesity risk. HK can be useful for federal nutrition programs for evaluation, risk assessment, goal setting, and/or program planning in clinical and community environments.

The effects of diurnal intermittent fasting on proinflammatory cytokine levels while controlling for sleep/wake pattern, meal composition and energy expenditure.

PURPOSE: This study aimed to assess the effect of diurnal intermittent fasting (DIF) during and outside of the month of Ramadan on plasma levels of interleukin (IL)-1ß, IL-6, and IL-8, while controlling for sleep/wake pattern, sleep length and quality, meal composition, energy consumption and expenditure, and light exposure. DIF outside of the month of Ramadan was performed to evaluate the effect of DIF in the absence of the way of life accompanying Ramadan. METHODS: Twelve healthy male volunteers with a mean age of 25.1 ± 2.5 years arrived to the sleep laboratory on 4 times: 1) adaptation, 5 weeks before Ramadan; 2) 4 weeks before Ramadan while performing DIF for 1 week (fasting outside of Ramadan; FOR); 3) 1 week before Ramadan (non-fasting baseline; non-fasting BL); and 4) After completing 2 weeks of Ramadan while performing DIF. Plasma levels of cytokines were assessed using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. RESULTS: During DIF, there was a significant decrease in the levels of cytokines, particularly, IL-1ß and IL-6, in most measurements compared to non-fasting BL. This reduction was more obvious during the FOR period. There were no significant changes in the circadian phase of the measured cytokines reflected by the acrophase of the measured variables during fasting (FOR and Ramadan) compared to non-fasting BL. CONCLUSION: Under controlled conditions, DIF led to significantly decreased plasma levels of cytokines (IL-1ß, IL-6, and IL-8), particularly IL-1ß and IL-6 across 24 h. DIF had no effect on the circadian patterns of the measured cytokines as shown by cosinor analysis.

Associations Between Maternal Experiences of Discrimination and Biomarkers of Toxic Stress in School-Aged Children.

OBJECTIVE: To examine associations between maternal experiences of discrimination and child biomarkers of toxic stress in a multiethnic, urban sample of mothers and children (4-9 years). METHODS: Data were drawn from a cross-sectional study of maternal-child dyads (N = 54) living in low-income neighborhoods in New Haven, Connecticut, USA. Mothers reported experiences of discrimination. Noninvasive biomarkers of toxic stress were collected to assess neuroendocrine (hair cortisol), immune (salivary cytokines, c-reactive protein), and cardiovascular (blood pressure) functioning in children. RESULTS: Maternal experiences of discrimination were associated with increased log-transformed salivary interleukin-6 (IL-6) levels in children (ß = 0.15, p = 0.02). CONCLUSIONS: Vicarious racism, or indirect exposure to discrimination experienced by caregivers, is associated with poor health outcomes for children. Immune pathways may be a biological mechanism through which racial discrimination "gets under the skin," but additional research is needed to fully understand these relationships. Uncovering the physiological mechanisms linking vicarious racism with child health is an important step towards understanding possible early roots of racial and ethnic health inequities.

Prevalence of scrub typhus in pyrexia of unknown origin and assessment of interleukin-8, tumor necrosis factor-alpha, and interferon-gamma levels in scrub typhus-positive patients.

BACKGROUND: Scrub typhus is lesser known cause of fever of unknown origin in India. Even if there have been reports documenting the prevalence of scrub typhus in different parts of India, it is still an unknown entity, and clinicians usually do not consider it as differential diagnosis. The present study was performed to document the prevalence of scrub typhus among febrile patients in western part of Uttar Pradesh and to assess the clinical profile of infected patients on the one hand and knowledge, attitude, and practices among clinicians on the other. MATERIALS AND METHODS: A total of 357 adult patients with fever of more than 5-day duration were recruited. All patients underwent complete physical examination, and detailed clinical history was elicited as per predesigned pro forma. After primary screening to rule out malaria, enteric fever, and leptospirosis infection, secondary screening for scrub typhus was done by rapid screen test and IgM ELISA. RESULTS: Scrub typhus infection was positive in 91 (25.5%) cases. The most common symptoms among the patients were fever (100%), pain in abdomen (79.1%), pedal edema 56 (61.5%), rash 44 (48.3%), headache 44 (48.3%), vomiting 42 (46.1%), constipation 33 (36.2%), cough 28 (30.7%), and lymphadenopathy 20 (21.9%). The median values of interleukin-8, interferon-gamma, and tumor necrosis factor-alpha in healthy controls were 15.54 pg/ml, 7.77 pg/ml, and 54.1 pg/ml, respectively, while the median values of these cytokines in scrub typhus-positive patients were 21.04 pg/ml, 8.74 pg/ml, and 73.8 pg/ml, respectively. CONCLUSION: Our results highlight that scrub typhus infection is an important cause of pyrexia of unknown origin, and active surveillance is necessary to assess the exact magnitude and distribution of the disease.

Predictive value of multiple cytokines and chemokines for mortality in an admixed population: 15-year follow-up of the Bambui-Epigen (Brazil) cohort study of aging.

Inflammation, particularly elevated IL-6 serum levels, has been associated with increased mortality risk, mostly in Caucasians. The influence of genetic ethno-racial background on this association is unknown. We examined associations between baseline serum levels of Interleukin-6 (IL-6) and other cytokines (IL1-2, TNF, IL-10, and IL1ß) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) with 15-year mortality in 1,191 admixed Brazilians aged 60years and over. Elevated IL6 level (but not other biomarkers) was associated with increased risk of deaths with fully adjusted hazard ratios of 1.51 (95% CI=1.15, 1.97), 1.54 (95% CI=1.20, 1.96) and 1.79 (95% CI=1.40, 2.29) for the 2nd, 3rd and the highest quartiles, respectively. Genomic African and Native American proportions did not modify the association (p>0.05). The discriminatory ability to predict death of a model based on IL-6 alone was similar as that of a comprehensive morbidity score (C statistics=0.59 and 0.60, respectively). The abilities of IL-6 and the morbidity score models to predict death remained stable for very long term after the baseline measurement. Our results indicate that genome-based African and Native American ancestries have no impact on the prognostic value of IL-6 for mortality.

Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in HCV patients as a prototype to monitor immunotherapy of infectious diseases.

In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.

Assessment of the Role of Metabolic Determinants on the Relationship between Insulin Sensitivity and Secretion.

BACKGROUND: Insulin secretion correlates inversely with insulin sensitivity, which may suggest the existence of a crosstalk between peripheral organs and pancreas. Such interaction might be mediated through glucose oxidation that may drive the release of circulating factors with action on insulin secretion. AIM: To evaluate the association between whole-body carbohydrate oxidation and circulating factors with insulin secretion to consecutive oral glucose loading in non-diabetic individuals. METHODS: Carbohydrate oxidation was measured after an overnight fast and for 6 hours after two 3-h apart 75-g oral glucose tolerance tests (OGTT) in 53 participants (24/29 males/females; 34±9 y; 27±4 kg/m2). Insulin secretion was estimated by deconvolution of serum C-peptide concentration, ß cell function by mathematical modelling and insulin sensitivity from an OGTT. Circulating lactate, free-fatty acids (FFA) and candidate chemokines were assessed before and after OGTT. The effect of recombinant RANTES (regulated on activation, normal T cell expressed and secreted) and IL8 (interleukin 8) on insulin secretion from isolated mice islets was also measured. RESULTS: Carbohydrate oxidation assessed over the 6-h period did not relate with insulin secretion (r = -0.11; p = 0.45) or ß cell function indexes. Circulating lactate and FFA showed no association with 6-h insulin secretion. Circulating chemokines concentration increased upon oral glucose stimulation. Insulin secretion associated with plasma IL6 (r = 0.35; p<0.05), RANTES (r = 0.30; p<0.05) and IL8 (r = 0.41; p<0.05) determined at 60 min OGTT. IL8 was independently associated with in vivo insulin secretion; however, it did not affect in vitro insulin secretion. CONCLUSION: Whole-body carbohydrate oxidation appears to have no influence on insulin secretion or putative circulating mediators. IL8 may be a potential factor influencing insulin secretion.

Effect of the menopausal transition and physical activity energy expenditure on inflammatory markers: a MONET group study.

OBJECTIVE: Menopausal transition is usually associated with changes in body composition and a decrease in physical activity energy expenditure. Adipose tissue, especially visceral fat, is an important source of inflammatory markers, which contributes to the development of a proinflammatory state. Conversely, high levels of physical activity and exercise have an anti-inflammatory effect. This study aimed to investigate the impact of menopausal transition and physical activity on inflammatory makers. METHODS: One hundred two healthy premenopausal women participated in a 5-year longitudinal study. The present secondary analyses were performed on 58 participants with a full set of data (age: 49.6 ±â€Š1.7 y; body mass index: 23.3 ±â€Š2.4 kg/m). Measures included body composition, waist circumference, fasting glucose and insulin levels, insulin sensitivity, plasma lipid levels, cardiorespiratory fitness, physical activity energy expenditure, and inflammatory markers. RESULTS: Repeated measure analyses revealed, after the 5-year follow-up, significant increases in ferritin, interleukin-8 (IL-8), and soluble tumor necrosis factor-α receptor 1 and 2 (sTNFR1 and sTNFR2) (P < 0.001), and a significant decrease in serum high-sensitive C-reactive protein (P < 0.05). Positive correlations were observed between change (year 5 to baseline) in waist circumference and changes in high-sensitive C-reactive protein, orosomucoid (ORM), haptoglobin, and apolipoprotein B (ApoB) levels (0.26 ≤ r ≤ 0.34; P < 0.05), and between change in peripheral fat and changes in ORM, ApoB, sTNFR2 (0.28 ≤ r ≤ 0.39; P < 0.05). On the contrary, negative correlations were found between change in physical activity energy expenditure and changes in ORM as well as ApoB (r = -0.35 and r = -0.36, respectively; P < 0.05). No significant correlations were found between change in cardiorespiratory fitness, glucose, insulin, insulin sensitivity and changes in inflammatory markers. Multiple regression analyses showed that changes in physical activity energy expenditure and waist circumference together explained 23% of the individual variance of change in ORM (P < 0.05). Also, change in physical activity energy expenditure explained 15% (P < 0.05) of the variance of change in ApoB. Fat mass change explained 15% (P < 0.05) of the variance of change in IL-8, and finally change in peripheral fat explained 15% of variance of change in sTNFR2 (P < 0.05). CONCLUSIONS: The present study indicates that the menopausal transition is accompanied by an increase in inflammatory markers, namely ferritin, IL-8, sTNFR1, and sTNFR2. The increase in IL-8 and sTNFR2 with menopause could be explained, in part, by changes in fat mass and peripheral fat, respectively.

Assessment of CCL2 and CXCL8 chemokines in serum, bronchoalveolar lavage fluid and lung tissue samples from dogs affected with canine idiopathic pulmonary fibrosis.

Canine idiopathic pulmonary fibrosis (CIPF) is a progressive disease of the lung parenchyma that is more prevalent in dogs of the West Highland white terrier (WHWT) breed. Since the chemokines (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 8 (CXCL8) have been implicated in pulmonary fibrosis in humans, the aim of the present study was to investigate whether these same chemokines are involved in the pathogenesis of CIPF. CCL2 and CXCL8 concentrations were measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) from healthy dogs and WHWTs affected with CIPF. Expression of the genes encoding CCL2 and CXCL8 and their respective receptors, namely (C-C motif) receptor 2 (CCR2) and (C-X-C motif) receptor 2 (CXCR2), was compared in unaffected lung tissue and biopsies from dogs affected with CIPF by quantitative PCR and localisation of CCL2 and CXCL8 proteins were determined by immunohistochemistry. Significantly greater CCL2 and CXCL8 concentrations were found in the BALF from WHWTs affected with CIPF, compared with healthy dogs. Significantly greater serum concentrations of CCL2, but not CXCL8, were found in CIPF-affected dogs compared with healthy WHWTs. No differences in relative gene expression for CCL2, CXCL8, CCR2 or CXCR2 were observed when comparing lung biopsies from control dogs and those affected with CIPF. In affected lung tissues, immunolabelling for CCL2 and CXCL8 was observed in bronchial airway epithelial cells in dogs affected with CIPF. The study findings suggest that both CCL2 and CXCL8 are involved in the pathogenesis of CIPF. Further studies are required to determine whether these chemokines might have a clinical use as biomarkers of fibrosis or as targets for therapeutic intervention.

Longitudinal assessment of inflammation in recipients of continuous-flow left ventricular assist devices.

BACKGROUND: The long-term effects of continuous-flow left ventricular assist device (CF-LVAD) support on trends of inflammatory markers over time are unknown. We examined the hypothesis that the levels of inflammatory markers in CF-LVAD recipients are higher than in healthy controls and that these levels increase over time with long-term CF-LVAD support. METHODS: We examined the levels of inflammatory markers longitudinally at baseline before CF-LVAD implantation and at 3, 6, and 9 months after implantation. We then compared the levels of inflammatory markers to those in a healthy control group. RESULTS: Compared with baseline values before CF-LVAD implantation, left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) decreased significantly at 3, 6, and 9 months after CF-LVAD implantation. Brain natriuretic peptide (BNP) levels dropped significantly after CF-LVAD implantation but did not normalize. Improvements in ejection fraction at 3, 6, and 9 months after CF-LVAD implantation did not reach significance. Monocyte chemoattractant protein-1, interferon γ-induced protein, and C-reactive protein levels were higher in the CF-LVAD recipients at each of the time points (baseline before CF-LVAD implantation and 3, 6, and 9 months after implantation) compared with levels in healthy controls. In CF-LVAD recipients, serum interleukin-8, tumour necrosis factor-α, and macrophage inflammatory protein-ß increased significantly at 9 months, and macrophage-derived chemokine increased at 6 months after CF-LVAD implantation compared with baseline. CONCLUSIONS: Despite improvements in LV dimensions and BNP levels, markers of inflammation remained higher in CF-LVAD recipients. High levels of inflammation in CF-LVAD recipients may result from heart failure preconditioning or the long-term device support, or both. Because inflammation may be detrimental to CF-LVAD recipients, future studies should determine whether inflammatory pathways are reversible.

Assessment of serum interleukin-8 as a sensitive serological marker in monitoring the therapeutic effect of levamisole in recurrent aphthous ulcers: a randomized control study.

AIM: The study was designed to evaluate the serum interleukin-8 (IL-8) levels in patients with recurrent aphthous ulcer (RAU) and monitor the immunomodulation and altered IL-8 levels by levamisole before therapy and after levamisole therapy. MATERIALS AND METHODS: This study was carried as a randomized case-control study involving a study group of 30 patients diagnosed as RAUs and given levamisole (vermisole 150 mg, od for 1 st 3 days of 3 weeks in a month and for 3 months with a gap of 1 week) and these patients were recalled after 3 months and were subjected for estimation of serum IL-8 levels. Control group had 20 age and sex matched individuals with no systemic illness and were not given any levamisole. Good compliance was reported at the end of the study. RESULTS: Mild gastric irritation was reported and when severe it was managed by H1 blocker. Patients were reviewed after 3 months. The follow-up data at each visit with respect to each other and to base-line values was calibrated using a Students t-test. Highly significant comparisons were obtained in the serum IL-8 between study and control groups before the onset of levamisole (t = 6.53, P ≤ 0.001). IL-8 levels reduced by 72% after levamisole was instituted in RAU patients and comparison was highly significant for before and after levamisole onset (t = 5.54, P ≤ 0.001). CONCLUSION: This study points to the effectiveness of levamisole as an effective adjunct therapy in the routine management of RAU.

Assessment of the performance of three multiplex array panels for the detection of circulating cytokines and chemokines in naive, LPS, and SEB-treated cynomolgus macaques.

To assess relative sensitivity for detection of cytokines and chemokines in cynomolgus serum samples, we tested three commercially available multiplex array kits using the Luminex® platform with sera from animals exposed by intravenous injection to 150 µg/kg staphylococcal enterotoxin B (SEB) or 20 µg/kg lipopolysaccharide (LPS). Each of these kits detected similar patterns of changes in circulating cytokines/chemokines in response to SEB or LPS stimulation, especially the induction of high amounts of interleukin (IL)-2 and interferon-gamma (IFN-γ) in response to SEB but not LPS. However, there were clear differences in sensitivity for particular analytes, especially for IL-10. Additional experiments that focused on one multiplex array kit demonstrated very low or undetectable levels of cytokines in naive cynomolgus macaques, except for highly variable background levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1ß. Therefore, multiplex array analysis of circulating cytokine/chemokine patterns was capable of detection of systemic activation of diverse immune cell subsets.

Assessment of interleukin-6, interleukin-8 and interleukin-18 count in the serum of IUGR newborns.

AIM: Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA). MATERIALS: Research was conducted at the Lodz Medical University Clinic of Neonatology during 2010-2011. Surveyed group consisted of 50 hypotrophic full-term infants of single pregnancies (average weight: 2329 ± 287 g); control group, enclosing 50 infants AGA (average weight: 3544 ± 2161 g). Both groups received average Apgar score of 9 points. Concentrations of analysed cytokines were marked between 4-6 hours after birth. The enzyme-linked immunosorbent assay (ELISA) test was used to determine interleukins concentrations. Study was prospective. Statistics on the data were conducted with the Kolmogorov-Smirnov test. Significance level: p < 0.05. RESULTS: Concentrations of IL-6 and IL-18 were elevated in the IUGR group in a statistically significant manner in comparison to the control group. CONCLUSIONS: An elevated level of IL-6 and IL-18 in the IUGR group, comparing to control group, signifies the existence of inflammation in the process of developing IUGR, therefore, screening tests estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in predicting the occurrence of IUGR and help preventing it.

Assessment of chemokine serum levels in epithelial ovarian cancer patients.

AIMS AND BACKGROUND: The study was undertaken to investigate CCL2/MCP-1, CCL3/ MIP-1α, CCL4/MIP-1ß, CCL5/RANTES and CXCL8/IL-8 women with epithelial ovarian cancer. METHODS AND STUDY DESIGN: Sixteen patients diagnosed with epithelial ovarian cancer and 18 healthy women with no evidence of malign neoplasia (control group) aged from 23 to 89 years (mean ± SEM, 58.7 ± 2.3) were included. The epithelial ovarian cancer patients underwent laparotomy and debulking surgery. Chemokines serum levels were measured by cytometric bead array. Statistical analysis was performed using Mann-Whitney and Kendall's tau. P <0.05 was considered statistically significant for all analyses. RESULTS: The tumor staging (FIGO) was classified into: I in 4 cases (25%), III in 5 cases (31.3%) and stage IV in 7 cases (43.8%). Sera chemokine dosages of CCL2/MCP-1 and CCL4/MIP-1ß were lower in epithelial ovarian cancer patients than in the control group (P = 0.021 and P = 0.030, respectively). No significant difference between groups was observed in the levels of CCL3/MIP-1α, CCL5/RANTES and CXCL8/IL-8. No association between the chemokines analyzed and tumor stage was found. The serum level of CCL4/MIP-1ß was correlated with CA-125. CONCLUSIONS: The study of serum levels of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES and CXCL8/IL-8 chemokines in epithelial ovarian cancer patients identified a down-regulation in CCL2/MCP-1 and CCL4/MIP-1ß, which suggests that the two chemokines may play an important role in the pathophysiology of ovarian cancer.

Comparative assessment of cytokines and other inflammatory markers for the early diagnosis of neonatal sepsis-a case control study.

OBJECTIVE: Cytokines (IL-6, IL-8 and TNF-α), sCD163, and C-reactive protein were serially measured in an attempt to identify a set of tests which can reliably confirm or refute the diagnosis of neonatal sepsis at an early stage. METHODS: One hundred neonates suspected to have sepsis on clinical grounds and who met the inclusion criteria were enrolled for the study. Based on the positive or negative blood culture reports they were classified as infected (n=50) and non-infected (n=50) neonates respectively. Fifty healthy neonates without any signs of sepsis were also included in the study as control group. The initial blood sample was taken on day 0 (at the time of sepsis evaluation) and two further samples were taken on days 1 and 2 for monitoring the clinical progress and response to treatment. In the control group the cord blood and 48 hours venous sample was collected. Plasma CRP (ng/ml), IL-6 (pg/ml), IL-8 (pg/ml), TNF-α (ng/ml) and sCD163 (ng/ml) were determined by double antibody method Enzyme Linked Immunosorbent Assay in all the three blood samples. RESULTS: The cut of levels for CRP at >19,689 ng/ml had a sensitivity of 68%, specificity of 92%, for IL-6 at >95.32 pg/ml had a sensitivity of 54%, specificity of 96%, for IL-8 at >70.86 pg/ml had a sensitivity of 78%, specificity of 70%, for sCD163 at >896.78 ng/ml had a sensitivity of 100%, specificity of 88% for the diagnosis of infection before antibiotics. TNF-α levels of >12.6 ng/ml showed 100% sensitivity and 72% specificity for the diagnosis of inflammation. CONCLUSION: The most powerful predictor to differentiate between the non-infected and infected neonates before antibiotics was sCD163. The most powerful indicator for evaluation of prognosis is IL-6. sCD163 can be used alone to screen for sepsis in neonates before the results of blood culture are received.

An updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment of fever during neutropenia in children with cancer.

BACKGROUND: Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. The role of biomarkers in predicting morbidity and mortality associated with FN in children has been explored with varying results. This systematic review identified, critically appraised and synthesized information on the use of biomarkers for the prediction of outcome of FN in children/young adults, updating a review of initial assessment and adding further analysis of their value at reassessment. METHODS: This review was conducted in accordance with the Centre for Reviews and Dissemination Methods, using 3 different random effects meta-analysis models. RESULTS: Thirty-seven studies involving over 4689 episodes of FN in children were assessed, including an additional 13 studies investigating 18 biomarkers in 1670 FN episodes since the original review. Meta-analysis was possible for admission C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 and interleukin-8 in their ability to detect significant infection. Marked heterogeneity exists, precluding clear clinical interpretation of the results. Qualitative synthesis of the role of serial biomarkers suggests their predictive ability may be more pronounced at 24 to 48 hours compared with admission. Direct comparisons of the discriminatory power of admission values of PCT and CRP showed PCT generally had a better discriminatory estimate of serious infection than CRP. CONCLUSIONS: There remains a paucity of robust and reproducible data on the use of biomarkers in prediction of serious infection in children with FN. Available evidence suggests PCT has better discriminatory ability than CRP and that the role of serial biomarkers warrants further study.

The assessment between IL-6 and IL-8 and anthropometric status in malnourished children.

PURPOSE: To evaluate the correlations between the pro-inflammatory interleukins IL-6 and IL-8 and the anthropometric measurements in malnourished vs. non-malnourished children. PATIENTS AND METHODS: We have examined 219 children from Pediatric Clinic I, University of Medicine and Pharmacy of Tirgu Mures, Romania, during January 1, 2012-March 1, 2013 and divided according to Body Mass Index (BMI kg/m(2)) in the following two groups: 164 with normal nutritional status - control group (BMI between -2SD and +2SD), and 55 children with malnutrition (BMI <-2SD). All the children were evaluated anthropometric: BMI, weight for age (W/A), height for age (H/A), mid-upper-arm circumference (MUAC), tricipital skinfold (TSF) and paraclinical: IL-6 and IL-8 levels. RESULTS: From 219 children, 25.1% were malnourished. The mean age was 5.16 years in malnourished. IL-6 and IL-8 mean levels were 2.54 pg/mL, respectively 6.83 pg/mL in malnourished and 6.02 pg/mL, respectively 9.06 pg/mL in non-malnourished. By statistically comparing IL-6 in malnourished group vs. control group, we observed decreased values (p<0.0001) and also significantly lower values for IL-8. We also obtained statistical differences between the two groups in BMI, W/A, MUAC and TSF. The BMI SD have an increasing trend line, from -4SD in newborn malnourished to -2SD in near 18-year-old malnourished; the trend line had only a slight ascension in non-malnourished children. CONCLUSIONS: The interleukin levels and BMI, W/A, MUAC and TSF are significantly lower in malnourished children than in non-malnourished. This functional impairment may be involved in the malnutrition to develop a specific immune response in these children.

Prevalence of leptospira in acute hepatitis syndrome and assessment of IL-8 and TNF-alpha level in leptospiral hepatitis.

To study the prevalence of leptospira in acute hepatitis syndrome and to assess interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha levels in the pathogenesis of hepatitis due to leptospiral infection. Two hundred and forty-seven consecutive cases with symptoms of acute hepatitis and 30 healthy controls were enrolled in the study and detailed clinical history was elicited from them. Enzyme-linked immunosorbent assays (ELISAs) for HAV, HBV, HCV and HEV were performed to rule out common viral aetiology of hepatitis. IgM antibodies to leptospira were detected by ELISA. IL-8 and TNF-alpha levels were estimated in leptospira-positive cases and healthy controls by ELISA. Out of 247 cases of acute hepatitis, 46 (18.62%) were observed to be positive for IgM antibodies for leptospira. The mean age of these patients was 31.99 ± 0.28 years (25 males and 21 females; M/F ratio: 1.19:1). The mean ALT, AST and ASP were raised in the majority of patients. IL-8 was found to be elevated (130.81 pg/ml) in a large majority of cases 41/46, 89.1% (P < 0.001). Patients with more severe symptoms were associated with higher levels of IL-8. One mortality was observed due to leptospira. Unpredictably, TNF-alpha level was largely suppressed (45.63 pg/ml) in most of the leptospira-positive patients in comparison with healthy controls. Leptospira-induced hepatitis should be actively looked for in patients negative for A-E viral hepatitis. IL-8 appears to play an important role in the pathogenesis of leptospiral hepatitis. High TNF-alpha should alert clinicians for aggressive in hospital management of patients.