Elevated Serum Interleukin-6 Research Articles

Interleukin in endometriosis-associated infertility-pelvic pain: systematic review and meta-analysis.

The objective is to study the significance of altered interleukin levels in endometriosis-related infertility or pelvic pain. The present systematic review and meta-analysis includes a discussion on the roles of interleukin in the physiopathology of endometriosis-associated infertility and/or pelvic pain. We included all studies in which interleukins in peritoneal fluid, follicular fluid or serum from patients were measured and that correlated the findings with either peritoneal or deep endometriosis-associated infertility or pelvic pain. For the meta-analysis, we selected studies on the following cytokines: interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8). Endometriosis is a chronic inflammatory disease. Inflammatory processes clearly participate in the etiology of endometriosis. Cytokines are mediators of inflammation, and increase in their concentration in plasma or other body fluids signals the presence and extent of tissue lesions. A number of studies have reported on the association between higher cytokine levels and progression or maintenance of endometriosis and coexisting infertility or pelvic pain. The results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility. Such association was not found for endometriosis-associated pain. In spite of accumulated evidence on the association of pro-inflammatory cytokines and endometriosis, it still is not clear if and how these mediators participate in the physiopathology of endometriosis-associated infertility or pelvic pain, in part due to poor quality of the evidence established in the vast majority of interleukins and challenges in endometriosis research reproducibility. In summary, the results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility.

Elevated Serum Ferritin and Interleukin-6 Level as the Risk Factor in Preterm Labor


 Objective : To investigate the association ofserum ferritin and Interleukin-6 (IL-6) elevation as the risk factors for preterm labor.
 Method : This study was a case-control study conducted at the Obstetrics and Gynecology Outpatient and Emergency Department at Sanglah General Hospital Denpasar, Bali in November 2014 until June 2015. The sample selection was done by consecutive sampling with total sample as many as 20 case samples (women with preterm labor) and 20 control samples (women with normal preterm pregnancy).
 Results : Based on the analysis, there was no significant difference of patient demografic such as age, gestational age, and parity among the two groups. Chi-square analysis showed that the increased serum ferritin level had 5 fold increased risk of developing preterm labor (OR = 4.89, 95% CI = 1.20-19.94; p = 0.022), and increased serum IL-6 level had 9 fold increased risk of developing preterm labor (OR = 9.33, 95% CI = 2.18-39.96; p = 0.001) compared to normal preterm pregnancy.
 Conclusion : It can be concluded that level of IL-6 and serum ferritin was the risk factor for preterm labor.
 Keywords: Interleukin-6, preterm labor, serum ferritin
 
 Abstrak 
 Tujuan :Untuk membuktikan hubungan kadar ferritin dan Interleukin-6 (IL-6) serum yang tinggi sebagai faktor risiko terjadinya persalinan preterm. 
 Metode :Penelitian ini bersifat observasional dengan studi case-control yang dilakukan di Poliklinik dan IRD Kebidanan dan Penyakit Kandungan RSUP Sanglah Denpasar, yang dilakukan mulai bulan November 2014 hingga Juni 2015. Pemilihan sampel dilakukan dengan cara berurutan dengan sampel penelitian sebanyak 20 sampel kasus (ibu dengan persalinan preterm) dan 20 sampel kontrol (ibu hamil preterm normal). 
 Hasil :Tidak didapatkan perbedaan bermakna dari demografik pasien yaitu usia, umur kehamilan, dan paritas pada kedua kelompok. Analisa chi-square menunjukkan peningkatan kadar ferritin serum memiliki peningkatan risiko 5 kali terjadinya persalinan preterm (OR = 4,90, IK 95% = 1,20-19,94; p = 0,022), dan peningkatan kadar IL-6 serum memiliki peningkatan risiko 9 kali terjadinya persalinan preterm (OR = 9,33, IK 95% = 2,18-39,96; p = 0,001) dibandingkan dengan kelompok ibu hamil preterm normal. 
 Kesimpulan : Kadar feritin dan IL-6 serum adalah faktor risiko terjadinya persalinan preterm. 
 Kata kunci: Interleukin-6, persalinan preterm, ferritin serum

A Case of Secondary Hemochromatosis with Elevated Serum Interleukin-6

A Case of Secondary Hemochromatosis with Elevated Serum Interleukin-6

Prognostic Significance of IL-6 in Hodgkin Lymphoma

Elevated serum interleukin-6 (IL-6) in Hodgkin lymphoma (HL) is reported to correlate with B symptoms, response rate and survival in adult patients. The authors studied prognostic significance of IL-6 expression by immunohistochemistry on Hodgkin-Reed Sternberg cells and background reactive cells in a retrospective cohort of pediatric HL patients treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) from January 2009 through December 2013. Of 142 patients, tissue blocks were retrieved in 110 patients. On logistic regression analysis, IL-6 expression on background cells alone was among the factors associated with inferior response rate (OR-9.9, 95%CI-1.2, 78.3; p = 0.03). On multivariate analysis, IL-6 expression on background cells alone had significant impact on 5 y freedom from treatment failure (FFTF) (HR-7.7, 95% CI-1.2, 48.6; p = 0.03). IL-6 expression by immunohistochemistry in the background cells is an independent poor predictor of response and FFTF in pediatric HL. Further prospective studies in children are needed to confirm the current findings and whether IL-6 expression can be used to stratify treatment.

PM2.5 exposure induces systemic inflammation and oxidative stress in an intracranial atherosclerosis rat model.

Exposure to airborne particle (PM2.5 ) is a risk factor for intracranial atherosclerosis (ICA). Because of the established role of systemic inflammation and oxidative stress by PM2.5 , we determined whether these processes account for PM2.5 -mediated ICA, and also whether omega-3 fatty acid (O3FA) dietary supplementation could attenuate them. Adult Sprague-Dawley rats were exposed to filtered air (FA) or PM2.5 and fed either a normal chow diet (NCD) or a high-cholesterol diet (HCD), administered with or without O3FA (5 mg/kg/day by gavage) for 12 weeks. The lumen and thickness of the middle cerebral artery (MCA) were assessed. Serum tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL-1β), and interferon gamma (IFN-γ) were detected by ELISA. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) activity, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, mRNA levels of Nrf2, HO-1, NQO-1, and protein level of NOX subunit gp91 were quantified to determine the oxidative profile of brain vessels. PM2.5 increased (P < .05) ICA, especially in the HCD group; elevated serum TNF-α, IL-6, IL-1β, and IFN-γ; increased cerebrovascular ROS, MDA, NOX activity, and gp91 protein levels; and decreased cerebrovascular SOD activity. Nrf2, HO-1, and NQO-1 mRNA levels were upregulated (P < .05) by PM2.5 exposure, especially in the HCD group. O3FA attenuated (P < .05) PM2.5 -induced systemic inflammation, vascular oxidative injury, and ICA. PM2.5 exposure induced systemic inflammation, cerebrovascular oxidative injury, and ICA in rats with HCD. O3FA prevented ICA development, and may therefore exert a protective effect against the atherogenic potential of PM2.5 .

Factors Predicting the Response to Cyclosporin Treatment in Patients With Chronic Spontaneous Urticaria: A Systematic Review.

PurposeThis study aimed to systemically review literature relating to factors that could potentially predict a favorable response to cyclosporine A (CsA) treatment for chronic spontaneous urticaria (CSU).MethodsA systematic literature review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.ResultsA total of 13 studies (404 patients with CSU and 200 healthy patients) were included. There were only 1 randomized controlled trial (RCT) and 12 non-RCTs. Our systematic review showed that positive autologous serum skin test results, positive baseline basophil histamine release assays, positive baseline basophil activation test responses, elevated baseline plasma D-dimer levels, elevated baseline serum interleukin (IL)-2, IL-5, and tumor necrosis factor-alpha (TNF-α) levels, and low baseline serum IgE levels might assist in predicting favorable CsA responses in CSU patients. Decreased plasma D-dimer levels; and decreased serum IL-2, IL-5, and TNF-α levels were reported to be correlated with clinical improvement after CsA treatment.ConclusionsSince most positive results were from non-RCT articles and some data were still inconsistent, this systematic review identified no reliable practical biomarker for predicting CsA treatment response in patients with CSU. There were no positive predictors with good consistency and mechanical plausibility.

A systematic review and meta-analysis of evaluation of serum interleukin 8 levels in hepatocellular carcinoma.

Aim of the studyTo estimate serum interleukin 8 (IL-8) level in patients with hepatocellular carcinoma (HCC) compared to controls and patients with chronic hepatitis (CH) and liver cirrhosis (LC).Material and methodsThree databases, i.e. PubMed, Web of Science, and Scopus, were searched up to November 2017 without language restriction. The mean difference (MD) and 95% confidence interval (CI) were used by a random-effects analysis in RevMan version 5.3, and sensitivity analysis was performed as the secondary analysis.ResultsOut of 239 studies found, 10 studies recruiting 659 HCC patients, 237 controls, 357 patients with LC, and 48 patients with CH were included and analyzed in the meta-analysis. The pooled MDs were 39.48 (95%CI: 152.31, 406.47, p < 0.00001), 21.32 (95% CI: –6.04, 48.68, p = 0.13), and 36.46 (95% CI: 21.77, 51.15, p < 0.00001) in the patients with HCC compared to the controls, the patients with LC and those with CH, respectively.ConclusionsAn elevated serum IL-8 level in the HCC patients compared to the three other groups showed an increased risk for this cytokine in HCC patients. Therefore, this interleukin can be used as a new biomarker replacing alpha-fetoprotein (AFP) or as a clinical assay for evaluation of the pathogenesis and probably the progression or development of HCC.

Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis

BackgroundSymptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS). MethodsIL-6 serum levels at disease onset were retrospectively analyzed in 24 infants suffering from NEC as well as 16 neonates with LOS. ResultsIL-6 serum levels at disease onset were significantly higher in infants suffering from NEC necessitating surgical intervention in the disease course compared to infants with medical NEC (5000 [785–5000] vs. 370 [78–4716] pg/ml, p = 0.0008) as well as gram-positive LOS (5000 [785–5000] vs. 84 [12–269] pg/ml, p = 0.0001). Infants suffering from gram-negative LOS exhibited elevated IL-6 serum levels at disease onset comparable to infants with surgical NEC (5000 [1919–5000] vs. 5000 [785–5000] pg/ml, p = 1.00). ConclusionThe proinflammatory cytokine IL-6 appears to be a promising marker to distinguish surgical NEC from medical NEC at the onset of disease but cannot discriminate between surgical NEC and gram-negative LOS. Level of evidenceII

Leukocyte Phenotype Is Altered in Peripheral Arterial Disease

Peripheral arterial disease (PAD) is characterized by low-grade systemic inflammation. Monocytes and monocyte-derived macrophages (MDMs) play a central role in vascular inflammation and its resolution. We hypothesize that impaired resolution in PAD contributes to adverse clinical outcomes. In a cross-sectional study, we profiled serum cytokines, phagocytic activity of leukocytes, monocyte cell surface markers, and gene expression of MDM from healthy individuals (n ≥ 10) and patients with stable claudication (n ≥ 10). Leukocyte phagocytosis of fluorescently labeled Escherichia coli and monocyte surface markers were determined by flow cytometry. MDMs were cultured from peripheral blood monocytes isolated by density gradient centrifugation. MDM cytokine production and gene expression, before and after stimulation with lipopolysaccharide, were determined by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Patients with PAD had elevated serum high-sensitivity C-reactive protein (3.7 vs 0.6 mg/L; P = .004) and interleukin (IL) 6 (5.1 vs 1.1 pg/mL; P = .01) and trended toward higher levels of monocyte chemoattractant protein 1 and lower adiponectin compared with healthy individuals. Circulating monocytes and polymorphonuclear cells (PMNs) from PAD patients had reduced phagocytic activity for E. coli (monocytes, >30% [P < .001]; PMNs, >25% [P < .01]). Flow cytometry demonstrated a higher proportion of the proinflammatory intermediate monocyte subset (CD14++16+, 1.8-fold; P = .04) in PAD subjects. MDMs from PAD patients retain their intrinsic inflammatory program, producing more IL-6 (>4-fold; P = .03) and IL-1β (>10-fold; P = .04) and demonstrating increased expression of M1 genes (tumor necrosis factor α, monocyte chemoattractant protein 1, CXCL10) and decreased expression of M2 genes (CCL17, MRC1) vs healthy individuals (Table). Clinically stable PAD patients have elevated serum inflammatory markers compared with healthy individuals. Circulating monocytes and PMNs in patients with PAD have reduced phagocytic activity and a greater proportion of the proinflammatory intermediate monocyte subset. MDMs from PAD patients preserve their elevated inflammatory state in culture. These data demonstrate a heightened inflammatory and impaired resolution phenotype in PAD that has potential implications for disease progression and response to interventions.TableMonocyte-derived macrophage (MDM) gene expression of the peripheral arterial disease (PAD) cohort vs healthy individualsGeneMl or M2PAD patients relative to healthy individualsExpression fold changeP valueTNF-α (veh)Ml2.71.02aTNF-α (LPS)0.81.33MCP-1 (veh)Ml1.92.05aMCP-1 (LPS)1.91.01aiNOS (veh)Ml1.34.26iNOS (LPS)1.04.94CXCL10 (veh)Ml7.87.04aCXCL10 (LPS)1.8129IL-10 (veh)M21.50.19IL-10 (LPS)2.72.009aCCL17 (veh)M20.48.09CCL17 (LPS)022.14MRC1 (veh)M20.52.09MRC1 (LPS)0.30.01aCCL17, Chemokine (C-C motif) ligand 17; CXCL10, C-X-C motif chemokine 10; IL-10, interleukin 10; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein 1; MRC1, mannose receptor C type 1; TNF-α, tumor necrosis factor α; veh, vehicle.Expression fold change was calculated as 2ˆ(–ΔΔCT) and represents the fold change in the average expression of the target gene within the PAD cohort (n = 10) vs the average expression of the target gene within the cohort of healthy individuals (n = 10), normalized to the housekeeping gene (HPRT). MDMs were stimulated with lipopolysaccharide to mimic the occurrence of an acute inflammatory event or vehicle for 24 hours before assessment of gene expression.aP < .05 by unpaired Student t-test. Open table in a new tab

MiR-93 blocks STAT3 to alleviate hepatic injury after ischemia-reperfusion.

Signal transducer and activator of transcription 3 (STAT3) is correlated with ischemia-reperfusion (I-R) injury. The previous studies showed a decreased miR-93 expression after I-R injury of heart or brain organs, but without knowledge in liver tissues. This study aims to investigate effects of MiR-93 on the hepatic injury after ischemia/reperfusion. Rat liver I-R model was generated. Liver function indexes including alanine transaminase (ALT) and aspartate aminotransferase (AST) were quantified, and serum tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels were quantified. Hepatic tissue apoptosis was measured by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and expression of microRNA-93 (miR-93), STAT3, and phosphorylated STAT3 (p-STAT3) were measured. Dual luciferase reporter gene assay confirmed targeted relationship between miR-93 and STAT3. Agomir or miR-93 agomir was injected into the peritoneal cavity of I-R model, followed by ALT and AST assays. Serum levels of TNF-α, IL-1β, and IL-6 were measured, followed by TUNEL assay for comparing STAT3 and p-STAT3 expression. Comparing to sham group, I-R group rat showed significantly elevated serum ALT, AST, TNF-α, IL-1β, and IL-6 contents, along with significantly elevated hepatic cell apoptosis, plus decreased miR-93 expression, whilst STAT3 and p-STAT3 expression was enhanced. Intraperitoneal injection of miR-93 agomir significantly decreased STAT3 or p-STAT3 expression, and decreased cell apoptotic rate. Serum levels of ALT, AST, TNF-α, IL-1β, and IL-6 were significantly decreased, accompanied by improved liver function. Hepatic I-R injury is accompanied by miR-93 down-regulation, plus STAT3 up-regulation. Overexpression of miR-93 significantly depressed STAT3 expression in liver I-R injury, alleviated hepatic injury or apoptosis, decreased inflammatory response, and improved liver function.

2-Phenylnaphthyridin-4-one Derivative LYF-11 Inhibits Interleukin-6-mediated Epithelial-to-Mesenchymal Transition via the Inhibition of JAK2/STAT3 Signaling Pathway in MCF-7 Cells.

Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial-mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells. MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells. In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6-induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway.

Association of serum interleukin-10, interleukin-17A and transforming growth factor-α levels with human benign and malignant breast diseases.

Interleukin-10 (IL-10), interleukin-17A (IL-17A) and transforming growth factor α (TGF-α) have been implicated in the progression of breast cancer. However, the diagnostic and prognostic roles of these cytokines in ductal carcinoma remain unclear. The present study therefore aimed to determine the serum levels of IL-10, IL-17 and TGF-α in subjects with benign and malignant breast diseases and to evaluate the clinical significance of these cytokines in ductal carcinoma. Pre-operative serum samples were collected from 378 patients with breast disease and 70 healthy subjects. IL-10, IL-17A and TGF-α levels were measured using ELISA. Serum levels of these cytokine in patients with different breast diseases were evaluated. Furthermore, correlations between levels of these cytokines and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in ductal carcinoma were determined. The results demonstrated that serum levels of IL-10 and IL-17A were significantly increased in subjects with atypical hyperplasia and ductal carcinoma. Furthermore, IL-10 and IL-17A levels were increased in patients with a more serious clinical tumor stage and tumors that were ER- and PR-. Furthermore, high serum levels of TGF-α were associated with HER2+ tumors. A strong positive correlation was identified between TGF-α and IL-17A levels. Therefore, the results of the current study revealed that elevated serum IL-10, IL-17A and TGF-α levels are strongly associated with ductal carcinoma, specifically with tumor stage. High serum levels of IL-10 and IL-17A were also associated with the negative expression of ER and PR in ductal carcinoma, and high serum levels of TGF-α were associated with the positive expression of HER2 in ductal carcinoma. Thus, serum cytokine levels may be measured to identify patients with a poor prognosis who may benefit from more aggressive management and treatment.

TRIM31 Deficiency Is Associated with Impaired Glucose Metabolism and Disrupted Gut Microbiota in Mice.

Tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase of the tripartite motif family, plays an important role in the innate immune response. It can reduce the activity of the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. However, little information is about glucose metabolic health of TRIM31-deficient mice, and investigations about gut microbiota in TRIM31-deficient mice is limited. Thus, we aimed to compare glucose metabolic parameters, gut microbiota composition and inflammatory cytokine levels between TRIM31−/− and wild-type (WT) mice, and further investigate whether or not certain gut microbiota taxon correlates with specific metabolic parameters and inflammation cytokines in TRIM31-deficient mice. TRIM31−/− mice showed glucose intolerance and insulin resistance, with a significant difference in gut microbiota composition, characterized by increased abundance of Prevotellaceae and Veillonellaceae. TRIM31−/− mice with impaired glucose metabolism was accompanied by elevated serum tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) concentrations, as well as upregulated caecal TNF-α, IL-1β, caspase-1, and NLRP3 expressions. Furthermore, elevated p-IRS-1/IRS-1 protein expression, and decreased Akt Thr308 phosphorylation were observed in TRIM31−/− mice. Prevotellaceae abundance was positively associated with caecal IL-1β mRNA expression, and Veillonellaceae was associated with higher TNF-α mRNA expression and serum insulin concentration. In conclusion, our study is novel in showing that TRIM31 deficiency is associated with impaired glucose metabolism and disrupted gut microbiota in mice. This study contributes to the theoretical foundation on the potential relationship between TRIM31 deficiency and the development of abnormal glucose metabolism.

Neonatal Leukemoid Reaction with Fetal Inflammatory Response Syndrome Is Associated with Elevated Serum Granulocyte Colony Stimulating Factor and Interleukin-6.

Leukemoid reaction (LR) is a reactive disease that exhibits abnormal blood values similar to leukemia, but not due to leukemia. One report showed that neonatal LR (NLR) was associated with elevated serum granulocyte colony stimulating factor (G-CSF) in only 30% of the study neonates. NLR is not always associated with the elevation of serum G-CSF. NLR was defined as a white blood cell count of ≥ 40 × 103/μL and/or blast cell concentration of > 2%. We have focused on NLR with fetal inflammatory response syndrome (FIRS), defined as a fetal systemic inflammatory reaction triggered by intrauterine infection. FIRS was diagnosed based on a cord serum interleukin-6 (IL-6) concentration ≥ 17.5 pg/mL and histopathological chorioamnionitis. Because NLR is highly associated with FIRS, we have hypothesized that NLR is associated with the elevation of both G-CSF and IL-6. This is the first report to measure multiple cytokines in NLR at the same time. The study comprised 19 preterm infants with FIRS: 8 with NLR (study group) and 11 without NLR (control group). Serum G-CSF and IL-6 concentrations were significantly higher in the study group than the control group. There was a positive correlation between G-CSF and IL-6 levels in the study group but not in the control group. These results suggest that elevated serum G-CSF and IL-6 may underlie NLR. Thus, G-CSF and IL-6 concentrations may be predictive of the onset of NLR. Measuring these cytokines is useful for judging the prognosis of preterm infants and for their post-natal clinical management.

Elevated Serum Interleukin-6 Predicts Favorable Response to Immunosuppressive Therapy in Children With Aplastic Anemia.

Immunosuppressive therapy (IST) is the standard treatment for aplastic anemia (AA) children who lack a sibling donor, but the clinical response rate to IST varies. Predictors of response to IST are valuable for stratifying AA patients and making clinical decisions. The serum interleukin (IL)-6 levels of 41 AA patients were measured at the time of diagnosis and the response rate of the patients to IST was evaluated at 3, 6, and 12 months after IST. Receiver-operator characteristic (ROC) analysis was used to calculate the predictive value of initial IL-6 levels in determining response at 6 months after IST. The initial IL-6 levels were significant higher in responders than nonresponders at 6 months after IST (211.89 vs. 18.09 pg/mL; P=0.005), using 36.8 pg/mL as a threshold, there were 80% sensitivity and 81% specificity for discriminating responders and nonresponders to IST. Patients with initial high IL-6 level (>36.8 pg/mL) have favorable response rates than those with initial low IL-6 level (<36.8 pg/mL) at 3, 6, and 12 months after IST (P<0.01). High levels of IL-6 at the time of diagnosis predict a favorable response to IST in children with AA and this may be helpful for patient's stratification and clinical decisions.

Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice.

Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and lactate dehydrogenase (LDH) activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

Elevated serum interleukin-6 is predictive of coronary artery disease in intermediate risk overweight patients referred for coronary angiography

BackgroundInterleukin-6 (IL-6) plays a central role in atherosclerosis and inflammation. It may improve risk prediction in patients at intermediate cardiovascular risk.ObjectiveTo analyze the impact of serum IL-6 in predicting early angiographic coronary artery disease in patients at intermediate cardiovascular risk with chest pain.MethodsIn a cross-sectional study, patients referred for coronary angiography due to suspected coronary artery disease (CAD) were included. Coronary artery disease was defined as the presence of at least 30% stenosis in one or more coronary artery. Severity of CAD was classified by the anatomic burden score. Performance of serum IL-6 assay was compared with ACC/AHA atherosclerotic cardiovascular disease (ASCVD) risk score and hs-CRP through receiver operating characteristic (ROC) curves.ResultsWe have included 48 patients with a mean 10-year ASCVD risk of 10.0 ± 6.8%. The prevalence of CAD was 72.9%. The presence of CAD was associated with higher mean levels of IL-6 (p = 0.025). Patients with CAD had significantly more overweight than subjects without CAD. In 27% of patients, IL-6 was >1.0 pg/mL and 100% of these patients had CAD, while only 64% in those with IL-6 <1.0 pg/mL, corresponding to a positive predictive value of 100% (p = 0.015). The area under the receiver operating characteristic (ROC) curve of IL-6, hs-CRP and ASCVD were respectively 0.72, 0.60 and 0.54. Intermediate risk patients with IL-6 >1.0 pg/mL were further reclassified into ASCVD high risk due to the presence of coronary lesions.ConclusionIn intermediate risk patients referred for coronary angiography, a serum IL-6 level above 1 pg/mL is predictive of significant CAD. IL-6 determination may be useful to reclassify ASCVD intermediate risk patients into higher risk categories.

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 IL1β) 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.

Elevated serum interleukin-10 level and M2 macrophage infiltration are associated with poor survival in angioimmunoblastic T-cell lymphoma.

Interleukin-10 (IL-10) induces an immunosuppressive microenvironment including M2 macrophages, inhibiting anti-tumor immunity. The aim of this study was to evaluate whether serum IL-10 level at diagnosis and tissue infiltration of M2 macrophages could predict survival outcome of patients with angioimmunoblastic T-cell lymphoma (AITL).We measured serum levels of IL-5, IL-10, IL-12, and interferon-gamma (IFN-γ) at diagnosis in AITL and other common subtypes of nodal T-cell lymphoma including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative anaplastic large cell lymphoma (ALCL) or ALK-positive ALCL between September 2008 and December 2014. We also analyzed the infiltration of CD68- and CD163-positive macrophages in tumor tissue of AITL. In total, 97 patients with AITL (n=37), PTCL-NOS (n=40), ALK-negative ALCL (n=11), or ALK-positive ALCL (n=9) were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Among cytokines, only the serum level of IL-10 was significantly higher in AITL patients than in other subtypes (P < 0.05). Compared to other subtypes, the association of serum IL-10 with overall survival (OS) was only significant in AITL. Accordingly, the response to CHOP chemotherapy was significantly worse in the high IL-10 group, and infiltration of CD163-positive M2 macrophages was significantly associated with OS in AITL. In conclusion, this study demonstrated the prognostic relevance of serum IL-10 and tissue infiltration of M2 macrophages in AITL patients. Our results suggest the possible use of these variables as potential therapeutic targets and novel prognostic indicators in patients with AITL.

Interleukin-6 Level among Iraqi Patients with Chronic Lymphocytic Leukemia from Babil Province

Introduction: Interleukin-6 (IL-6) is a pro-inflammatory cytokine and an anti-inflammatory myokine. Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. The exact role of IL-6 in CLL is still contraversial and needs alot of research.&#x0D; Aim of the study: To measure serum level of interleukin-6 among Iraqi patients from Babil province with a newly diagnosed untreated chronic lymphocytic leukemia and to assess it's association with the stage of the disease and peripheral blood indices.&#x0D; Materials and methods: This is a case-control study included 106 Iraqi patients with a newly diagnosed untreated chronic lymphocytic leukemia (CLL). They were from Babil province and attended the hospital during the period from 1st of November 2012 to 30th of October 2015, while the control group included 106 age and sex matched healthy individuals. CBC, blood film and serum IL-6 (Human IL-6 ELISA kit ) were done for both groups, and bone marrow exam was performed for the patients only.&#x0D; Results: The age of the patients ranged from 44 to 82 years with mean age of 61.8 ±6.14 years. Male:Female ratio was 1.8:1 and 57.5% of them were asymptomatic. Serum IL-6 was undetected in 39.6% (42/106) of the control cases and in 13.2% (14/106) of the patients; all of them were in CLL stages 0 and 1. Mean serum IL-6 in the patient group was 12.6 ±5.1 pg/ml, while it was 6.2 ±2.3 pg/ml in the control group (P-value was 0.001). Higher levels were documented in stages 3 and 4 (P-value 0.0001).&#x0D; Conclusion and recommendations: Elevated serum IL-6 was found among Iraqi patients with newly diagnosed untreated CLL, and higher levels were documented in advanced stage disease. Further studies are needed to assess exact role of IL-6 in CLL as it may have prognostic and/or therapeutic implications.