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Sample records for necrosis factor-alpha interleukin-6

  1. Plasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive Disorder

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    N. Konuk

    2007-01-01

    Full Text Available Aim. Recent research implicated place of an immune mechanism in the pathophysiology of obsessive-compulsive disorder (OCD. Despite increasing evidence involvement of cytokine release in OCD, results of the studies are inconsistent. The aim of this study was to evaluate the plasma levels of the cytokines; tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6 in OCD patients. Methods. Plasma concentrations of TNF-α and IL-6 were measured in 31 drug-free outpatients with OCD, and 31-year age and sex-matched healthy controls. TNF-α and IL-6 concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA. Results. Both TNF-α and IL-6 levels showed statistically significant increases in OCD patients compared to controls (P<.000, P<.001, resp.. In addition, the age of onset was negatively correlated with TNF-α level (r=−.402, P=.025 and duration of illness was weakly correlated with IL-6 levels (r:.357; P:.048 in patients group. Conclusion. OCD patients showed increases in TNF-α and IL-6 levels compared to the healthy controls. This study provides evidence for alterations in the proinflamatory cytokines which suggest the involvement of the immune system in the pathophysiology of OCD.

  2. Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer.

    Science.gov (United States)

    Brailo, Vlaho; Vucicevic-Boras, Vanja; Lukac, Josip; Biocina-Lukenda, Dolores; Zilic-Alajbeg, Iva; Milenovic, Aleksandar; Balija, Melita

    2012-01-01

    The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral cancer and healthy controls. Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay. Salivary IL-1β and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (pcancer patients. Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies.

  3. Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer

    Science.gov (United States)

    Vucicevic-Boras, Vanja; Lukac, Josip; Biocina-Lukenda, Dolores; Zilic-Alajbeg, Iva; Milenovic, Aleksandar; Balija, Melita

    2012-01-01

    Objectives: The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral cancer and healthy controls. Study design: Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay. Results: Salivary IL-1β and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (poral cancer patients. Conclusions: Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies. Key words: Cytokines, oral, leukoplakia, cancer. PMID:21743397

  4. Manipulation of flaxseed inhibits tumor necrosis factor-alpha and interleukin-6 production in ovarian-induced osteoporosis.

    Science.gov (United States)

    Abdelkarem, Hala M; Abd El-Kader, Madeha M; Kasem, Seham A

    2011-04-01

    To evaluate the potential effects of whole flaxseed (FS), and/or flax oil (FO) incorporation into the diet on the level of pro-inflammatory cytokines in ovariectomized (OVX) rats model of osteoporosis. This study was performed in the Food Science & Agriculture Collage, King Saud University, Kingdom of Saudi Arabia from October to December 2009. Forty-eight, 3-month-old female Sprague-Dawley rats were randomly divided into 6 groups: Group 1 - sham + control diet; Group 2 - OVX rats + basal diet; Group 3 - OVX + 20% whole FS; Group 4 - OVX rats + 40% FS; Group 5 - OVX rats + 5% FO; Group 6 - OVX rats + 10% FO. All OVX rats underwent bilateral ovariectomy. The experiment was continued for 2 months. Serum bone alkaline phosphatase (B-ALP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), calcium (Ca), phosphorous (P), and magnesium (Mg) were measured. A significant increase of serum IL-6 and TNF-alpha concentrations were observed between OVX rats when compared with Group 1, while there was no significant difference in the activity of B-ALP, serum Ca, P, and Mg among all groups. A remarkable significant decrease of serum levels of IL-6 and TNF-alpha was observed in the group of rats that were fed with FS (Groups 3 and 4) and FO (Groups 5 and 6). This study suggests that FS and FO might be useful in the prevention of estrogen-deficiency induced osteoporosis via decreasing osteoclastogenesis. Further studies are needed to demonstrate their efficacy in humans by using bioactive components of FS, and to clarify their mechanism of action.

  5. Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis

    International Nuclear Information System (INIS)

    Fida, Nadia M.; Fadelallah, Mohamed F.; Al-Mughales, Jamil A.

    2006-01-01

    To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n=28), meningitis (n=7), and healthy controls (n=16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n=6), group 2 = clinical sepsis (n=14), and group 3 = possible-infected (n=8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer: In sepsis and meningitis patients, serum levels of CRP (p<0.01, p<0.05,) and IL-1alpha (p<0.001, p<0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p<0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p<0.05, p<0.001, p<0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis. (author)

  6. The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

    DEFF Research Database (Denmark)

    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...

  7. The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

    DEFF Research Database (Denmark)

    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...

  8. Tumor necrosis factor-alpha and interleukin -6 as diagnostic markers of diabetic complications in children with type I diabetes mellitus

    International Nuclear Information System (INIS)

    El-Nashar, N.A.; Moawad, A.T.; Nassar, E.M.

    2010-01-01

    This study aimed to determine the role of cellular auto immunity and its humoral mediators in pathogenesis and following up of type I diabetes mellitus (TIDM). Therefore, serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), glycemic control, body mass index, duration of the disease and microalbuminuria in children with TIDM were evaluated. This study was conducted on 30 patients suffered from type I diabetes mellitus (TIDM), 14 males and 16 females with mean age of 11.40 ±3.67 years and 20 apparently healthy children served as control (10 male and 10 female). Children with TIDM were classified according to duration: diabetic children for 5 years or less duration (n= 15, duration means: 2.74 ± 1.34 years) and diabetic children > 5 years (n=15, duration means: 7.35 ± 1.49 years); according to glycemic control: children with good glycemic control (n=16, HbAIc: 7.82 ± 2.70) and diabetic children with poor glycemic control (n=14, HbAIc: 10.49 ± 2.72) and according to complication: diabetic children without complications (n= 20) and diabetic children with microvascular or neurological complications (n= 10, nephritic, retinal or neurological complications). Patients and controls were subjected to careful history, clinical examination and laboratory investigations. The following investigations were done for all children; random blood glucose, Glycated hemoglobin (HbAIc %), microalbuminuria and kidney function tests. Serum tumour necrosis factor-alpha (TNF-alpha) and serum interleukin-6 (IL-6) were measured using immuno-enzymometric assay (ELISA). Patients with TIDM with duration more than 5 years, with poor glycemic control and with complications had higher serum glucose levels, higher HbAIc%, higher level of blood urea nitrogen (BUN), serum creatinine, microalbuminuria and elevated serum TNF-alpha (p<0.0001) and IL-6 (p<0.0001) in comparison to the same diabetic patients with 5 years duration or less, with good glycemic control

  9. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

    DEFF Research Database (Denmark)

    Bruunsgaard, H; Ladelund, S; Pedersen, A N

    2003-01-01

    % of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate......Ageing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-alpha) initiates the inflammatory cascade and has been linked to several age-associated disorders. It remains, however, unknown if TNF-alpha is associated with mortality......-alpha and IL-6 on survival in the following 6 years. A total of 133 participants died during this follow-up period. TNF-alpha was associated with mortality in men, but not in women, whereas low-grade elevations in IL-6 were associated strongly with mortality in both sexes. TNF-alpha explained only 7...

  10. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

    DEFF Research Database (Denmark)

    Bruunsgaard, H; Ladelund, S; Pedersen, A N

    2003-01-01

    Ageing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-alpha) initiates the inflammatory cascade and has been linked to several age-associated disorders. It remains, however, unknown if TNF-alpha is associated with mortality...... in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF......% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate...

  11. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Ladelund, S.; Pedersen, Agnes Nadelmann

    2003-01-01

    Ageing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-alpha ) initiates the inflammatory cascade and has been linked to several age-associated disorders. It remains, however, unknown if TNF-alpha is associated with mortality...... in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF......% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate...

  12. Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum

    NARCIS (Netherlands)

    Prins, J. M.; Kuijper, E. J.; Mevissen, M. L.; Speelman, P.; van Deventer, S. J.

    1995-01-01

    The concentration and accessibility of endotoxin can increase following antibiotic killing of gram-negative bacteria. There are indications that antibiotics may differ in this respect. We measured endotoxin levels in RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 production

  13. ASTAXANTHIN MENURUNKAN KADAR VASCULAR ENDOTHELIAL GROWTH FACTOR, TUMOR NECROSIS FACTOR ALPHA, INTERLEUKIN-6, DAN NITRIC OXIDE PADA NONPROLIFERATIVE DIABETIC RETINOPATHY RINGAN: UJI KLINIS TERKENDALI

    Directory of Open Access Journals (Sweden)

    Ni Made Laksmi Utari

    2015-01-01

    Full Text Available Diabetic Retinopathy (DR merupakan komplikasi mikrovaskular pada Diabetes Mellitus (DM dan penyebab kebutaan paling sering pada usia produktif. Hiperglikemia menyebabkan terjadinya reaksiinflamasi dan stres oksidatif  dalam patogenesis DR dipaparkan oleh beberapa peneliti, namun peran antioksidan dalam mengurangi progresifitas DR masih menjadi perdebatan. Penelitian ini bertujuanuntuk mengetahui pemberian astaxanthin 8 mg dapat menurunkan kadar Vascular Endothelial Growth Factor (VEGF, Tumor Necrosis Factor-alpha (TNF-á, Interleukin-6 (IL-6 dan Nitric Oxide (NO padapenderita Non Proliferative Diabetic Retinopathy (NPDR ringan. Penelitian clinical trial dengan perluasan Randomized, Double Blinded, Placebo-Control, Pre and Posttest Group Design ini dilaksanakanpada bulan Juli 2013 - Desember 2013 di Poliklinik Mata RSUP Sanglah Denpasar Bali. Jumlah sampel yang memenuhi kriteria eligibilitas sebanyak 40 pasien NPDR ringan terbagi menjadi 20 pasien  sebagai kelompok perlakuan yang diberikan astaxanthin 8 mg dan 20 pasien NPDR ringan yang diberikan plasebo sebagai kelompok kontrol. Pengambilan sampel darah vena untuk pemeriksaan dilakukan sebelum dan setelah pemberian astaxanthin 8 mg serta plasebo selama 4 minggu. Perbedaan kadar rerata VEGF, TNF-á, IL-6 dan NO dianalisis dengan uji-t jika distribusi data normal dan uji Mann-whitney jika distribusi data tidak  normal. Hasil penelitian ini diharapkan dapat memberikaninformasi mengenai hubungan VEGF, TNF-á, IL-6, dan NO dalam perkembangan NPDR ringan serta manfaat pemberian astaxanthin dalam perkembangan NPDR ringan. [MEDICINA 2014;45:31-37

  14. Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha as a potential biomarker for recurrence in patients with oral squamous cell carcinoma.

    Science.gov (United States)

    Skrinjar, Ivana; Brailo, Vlaho; Vidovic-Juras, Danica; Vucicevic-Boras, Vanja; Milenovic, Aleksandar

    2015-07-01

    Oral squamous cell carcinoma (OSCC) constitutes 3 percent of all cancers with predominant occurrence in middle aged and elderly males. Tumour recurrence worsens disease prognosis and decreases quality of life in patients with OSCC. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) have been suggested to play a certain role in variety of tumours. The aim of this study was to investigate the relationship of pretreatment serum IL-6 and TNF-α levels on tumour recurrence in patients with OSCC in order to identify potential biomarkers for the early detection of disease recurrence. The patients with newly diagnosed OSCC were treated and followed from the first visit from November 2006 until January 2008. Serum IL-6 and TNF-α concentrations were measured. The records of the patients were re-examined in July 2012 and data were recorded about cancer characteristics and tumour recurrence. Disease free survival was analyzed by Kaplan-Meier survival curves, log rank test and Cox proportional hazards regression. Serum IL-6 was shown as an independent risk factor for tumour recurrence. Pretreatment serum IL-6 concentration may be a useful biomarker for identification of OSCC patients with increased risk of the disease recurrence.

  15. Serum biomarker profiles of interleukin-6, tumor necrosis factor alpha, matrix-metalloproteinase-2, and vascular endothelial growth factor in endometriosis staging

    Directory of Open Access Journals (Sweden)

    Wachyu Hadisaputra

    2013-05-01

    Full Text Available Background: The focus of this study was to compare serum biomarkers: interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, matrix-metalloproteinase-2 (MMP-2 and vascular endothelial growth factor (VEGF in endometriosis stage I-II and stage III-IV. Methods: This is a cross-sectional study. Forty endometriosis patients were diagnosed using laparoscopy procedure. Serum sample was taken before the surgery. The serum biomarkers (IL-6, TNF-α, MMP-2, and VEGF were analyzed with ELISA method at the end of research. Mean of serum biomarkers in endometrosis stage I-II and stage III-IV were compared using unpaired t-test. Variables that show significant mean difference were tested using ROC measurement and the optimal cut-off point was determined. Results: There was no significant difference in mean serum biomarkers level of IL-6, TNF-α, and MMP-2 between endometriosis stage I-II and stage III-IV (1.58 ± 0.78 vs 1.55 ± 0.98 pg/mL, 1.5 ± 0.47 vs 1.49 ± 0.29 pg/mL, and 152.04 ± 27.32 vs 140.98 ± 28.08 ng/mL, respectively. On the other hand, the comparison of VEGF level in endometriosis stage I-II and stage III-IV demonstrated significant difference (289.76 ± 188.13 vs 581.29 ± 512.85 pg/mL (p < 0.05. Mean difference of VEGF had AUC of 74.5%. Optimal cut-off point for VEGF was ≥ 314.75 pg/mL with sensitivity 78.6% and specificity 69.2%. Conclusion: This study showed that serum biomarkers of VEGF level (but not IL-6, TNF-α, and MMP-2 can be used to measure the degree of severity in endometriosis. VEGF level of 314.75 pg/mL represents the cut-off point between lower and higher stage of severity. (Med J Indones. 2013;22:76-82Keywords: Endometriosis, interleukin-6, matrix-metalloproteinase-2, TNF-α, vascular endhothelial growth factor

  16. Phase I study of bryostatin 1: assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. The Cancer Research Campaign Phase I Committee.

    Science.gov (United States)

    Philip, P A; Rea, D; Thavasu, P; Carmichael, J; Stuart, N S; Rockett, H; Talbot, D C; Ganesan, T; Pettit, G R; Balkwill, F

    1993-11-17

    Many oncogenes have been shown to code for growth factor receptors that are involved in regulation of cell growth and proliferation and can activate transcription via protein kinase C. Bryostatin 1, a partial agonist of protein kinase C, has demonstrated potent antitumor activity in vitro and in vivo in human tumor xenografts. The aim of this phase I study was to determine the optimal dosage and toxicity profile of bryostatin 1 and its influence on cytokine release in vivo. Three successive cohorts consisting of 35 patients with various malignant tumors were treated with bryostatin 1 by intravenous infusion over 1 hour as follows: cohort A--35 micrograms/m2 (three patients) or 50 micrograms/m2 (eight patients) once every 2 weeks; cohort B--25 micrograms/m2 once a week (eight patients); and cohort C--25 micrograms/m2 once a week for 3 weeks, with no treatment during the 4th week (16 patients). Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) were measured by immunoradiometric assay and by radioimmunoassay, respectively. The dose-limiting toxicity was grade 3 or 4 myalgia in four of 11 patients in cohort A, in two of eight in cohort B, and in none of 16 in cohort C. Occurrence of myalgia was dose related. There was no significant myelosuppression, apart from a small and transient fall in platelet count. Six patients experienced acute but transient skin flushing, dyspnea, hypotension, and bradycardia, probably related to the bryostatin 1 vehicle. TNF-alpha and IL-6 were detected in plasma at 2 and 24 hours after treatment, respectively, and the levels were dose related (P = .02). Two patients with metastatic malignant melanoma had partial remission after three or four cycles of therapy; remission lasted 6 weeks and 10+ months, respectively. The dose-limiting toxicity of bryostatin 1 was myalgia. Plasma IL-6 and TNF-alpha concentrations were increased within 24 hours of therapy. Antitumor activity against malignant melanoma was observed

  17. Effects of concurrent training on interleukin-6, tumour necrosis factor-alpha and C-reactive protein in middle-aged men.

    Science.gov (United States)

    Libardi, Cleiton Augusto; Souza, Giovana Verginia; Gáspari, Arthur Fernandes; Dos Santos, Claudinei Ferreira; Leite, Sabrina Toffoli; Dias, Rodrigo; Frollini, Anelena B; Brunelli, Diego Trevisan; Cavaglieri, Claudia Regina; Madruga, Vera Aparecida; Chacon-Mikahil, Mara P T

    2011-11-01

    The purpose of this study was to evaluate the effects of moderate- to high-intensity resistance and concurrent training on inflammatory biomarkers and functional capacity in sedentary middle-aged healthy men. Participants were selected on a random basis for resistance training (n = 12), concurrent training (n = 11) and a control group (n = 13). They performed three weekly sessions for 16 weeks (resistance training: 10 exercises with 3 × 8-10 repetition maximum; concurrent training: 6 exercises with 3 × 8-10 repetition maximum, followed by 30 minutes of walking or running at 55-85% [Vdot]O(2peak)). Maximal strength was tested in bench press and leg press. The peak oxygen uptake ([Vdot]O(2peak)) was measured by an incremental exercise test. Tumour necrosis factor-α, interleukin-6 and C-reactive protein were determined. The upper- and lower-body maximal strength increase for both resistance (+42.52%; +20.9%, respectively) and concurrent training (+28.35%; +21.5%, respectively) groups (P = 0.0001).[Vdot]O(2peak) increased in concurrent training when comparing pre- and post-training (P = 0.0001; +15.6%). No differences were found in tumour necrosis factor-α and interleukin-6 for both groups after the exercise. C-reactive protein increased in resistance training (P = 0.004). These findings demonstrated that 16 weeks of moderate- to high-intensity training could improve functional capacity, but did not decrease inflammatory biomarkers in middle-aged men.

  18. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

    LENUS (Irish Health Repository)

    Harmon, D

    2012-02-03

    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol\\/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg\\/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

  19. Changes in gene expression of tumor necrosis factor alpha and interleukin 6 in a canine model of caerulein-induced pancreatitis.

    Science.gov (United States)

    Song, Ruhui; Yu, Dohyeon; Park, Jinho

    2016-07-01

    Acute pancreatitis is an inflammatory process that frequently involves peripancreatic tissues and remote organ systems. It has high morbidity and mortality rates in both human and veterinary patients. The severity of pancreatitis is generally determined by events that occur after acinar cell injury in the pancreas, resulting in elevated levels of various proinflammatory mediators, such as interleukin (IL) 1β and 6, as well as tumor necrosis factor alpha (TNF-α). When these mediators are excessively released into the systemic circulation, severe pancreatitis occurs with systemic complications. This pathophysiological process is similar to that of sepsis; thus, there are many striking clinical similarities between patients with septic shock and those with severe acute pancreatitis. We induced acute pancreatitis using caerulein in dogs and measured the change in the gene expression of proinflammatory cytokines. The levels of TNF-α and IL-6 mRNA peaked at 3 h, at twice the baseline levels, and the serum concentrations of amylase and lipase also increased. Histopathological examination revealed severe hyperemia of the pancreas and hyperemia in the duodenal villi and the hepatic sinusoid. Thus, pancreatitis can be considered an appropriate model to better understand the development of naturally occurring sepsis and to assist in the effective treatment and management of septic patients.

  20. Contrasting effects of an ultraviolet B and an ultraviolet A tanning lamp on interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1 expression.

    Science.gov (United States)

    Clingen, P H; Berneburg, M; Petit-Frère, C; Woollons, A; Lowe, J E; Arlett, C F; Green, M H

    2001-07-01

    Recent studies have demonstrated that a tanning lamp emitting predominantly ultraviolet (UV) A induces significant yields of the type of potentially mutagenic DNA damage that are associated with the onset of skin cancer (i.e. cyclobutane pyrimidine dimers). UV-induced immunosuppression is also an important event leading to skin cancer. To the modulation of key immunological molecules following exposure to a broad-spectrum UVB lamp and a predominantly UVA-emitting tanning lamp using model in vitro systems. We compared secretion and mRNA expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in normal human epidermal keratinocytes, and interferon (IFN)-gamma-induced intracellular adhesion molecule (ICAM)-1 in normal human fibroblasts irradiated in vitro with a broad-spectrum UVB lamp or with a Philips 'Performance' tanning lamp. With broad-spectrum UVB irradiation, upregulation of IL-6 and TNF-alpha mRNA was detected 6 h after irradiation, and a dose-dependent increase of cytokines in the supernatants of irradiated cells was found 24 h after irradiation. In contrast, there was no cytokine secretion and little evidence for mRNA upregulation following exposure to a tanning lamp. When cells were exposed first to broad-spectrum UVB, then the tanning lamp, UVB-induced cytokine secretion was inhibited, although mRNA levels were upregulated to a level close to that observed with UVB alone. By using a Schott WG 320 nm filter to attenuate the level of UVB relative to UVA emitted by the tanning lamp, the inhibition of cytokine secretion was shown to be associated with UVA exposure. Both UV sources inhibited IFN-gamma-induced ICAM-1 mRNA expression in a dose-dependent fashion. By using a Schott WG 335 nm filter, inhibition of ICAM-1 mRNA expression by the tanning lamp was shown to be associated with UVB exposure. These results suggest that UV sources emitting different levels of UVA and UVB have differential effects on the modulation of different

  1. Normal Ranges for Acute Phase Reactants (Interleukin-6, Tumour Necrosis Factor-alpha and C-reactive Protein) in Umbilical Cord Blood of Healthy Term Neonates at the Mount Hope Women's Hospital, Trinidad.

    Science.gov (United States)

    Khan, A; Ali, Z

    2014-09-01

    To determine normal ranges for interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) in umbilical cord blood from healthy term neonates at the Mount Hope Women's Hospital (MHWH), Trinidad. A prospective cohort study was conducted on healthy pregnant women admitted to the MHWH during the period October 1 to December 31, 2010. Women who were term with no signs of or risk factors for sepsis were recruited into the study after informed consent was obtained. Data were collected including maternal age, antenatal and perinatal history. Umbilical cord blood samples were collected and analysed for IL-6, TNF-α and CRP. Ethical approval was obtained from the Ethics Committee, Faculty of Medical Sciences, The University of the West Indies, Trinidad and Tobago. One hundred and sixty-two samples from healthy term neonates were analysed for IL-6 and TNF-α. One hundred and thirty-one samples were analysed for CRP due to one faulty kit. There were almost equal numbers of males (55%) and females (45%). Ninety per cent were > 2500 g at birth and 10% had low birthweight. Reference ranges of 0-16.4 pg/ml, 0-29.4 pg/ml and 0-12.4 mg/L were found for IL-6, TNF-α and CRP, respectively with 95% confidence intervals (11.6, 21.5 pg/ml; 24.0, 33.1 and 8.4, 15.1, respectively). The normal ranges for IL-6, TNF-α and CRP in umbilical cord blood for healthy term Trinidadian neonates were 0-16.4 pg/ml, 0-29.4 pg/ml and 0-12.4 mg/L, respectively.

  2. A Meta-analysis on the Effect of Ulinastatin on Serum Levels of C-Reactive Protein, Interleukin 6, and Tumor Necrosis Factor Alpha in Asian Patients with Acute Pancreatitis.

    Science.gov (United States)

    Zhang, Chunze; Wang, Yijia; Fu, Wenzheng; Zhang, Weihua; Wang, Tao; Qin, Hai

    2016-03-01

    We aimed to investigate the influence of ulinastatin (UTI) on the serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in Asian patients with acute pancreatitis (AP) by performance of a meta-analysis. Two investigators independently searched 11 databases, including PUBMED, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Cochrane Library, Wanfang database, China National Knowledge Infrastructure (CNKI), Chinese Journal Full-text Database, and China Biomedicine Database. The full-text articles were screened and the data were extracted using a standardized data extraction form. All statistical analyses were conducted with Stata software, version 12.0 (Stata Corporation, College Station, TX). A total of 94 studies were initially retrieved, and 10 studies containing 424 Asian patients with AP were ultimately enrolled in this meta-analysis. The results revealed that the serum levels of CRP, IL-6, and TNF-α in Asian AP patients significantly decreased after UTI therapy (CRP: standardized mean difference [SMD] = 3.26, 95% confidence interval [CI] = 1.69-4.83, p < 0.001; IL-6: SMD = 5.92, 95% CI = 2.09-9.75, p = 0.002; TNF-α: SMD = 4.07, 95% CI = 0.79-7.35, p = 0.015). The results of this meta-analysis suggest that UTI can effectively depress the serum levels of CRP, IL-6, and TNF-α in Asian patients with AP, and thereby inhibit inflammation.

  3. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord.

    Science.gov (United States)

    Kawasaki, Yasuhiko; Zhang, Ling; Cheng, Jen-Kun; Ji, Ru-Rong

    2008-05-14

    Central sensitization, increased sensitivity in spinal cord dorsal horn neurons after injuries, plays an essential role in the induction and maintenance of chronic pain. However, synaptic mechanisms underlying central sensitization are incompletely known. Growing evidence suggests that proinflammatory cytokines (PICs), such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha), are induced in the spinal cord under various injury conditions and contribute to pain hypersensitivity. Using patch-clamp recordings in lamina II neurons of isolated spinal cord slices, we compared the effects of IL-1beta, IL-6, and TNFalpha on excitatory and inhibitory synaptic transmission. Whereas TNFalpha enhanced the frequency of spontaneous EPSCs (sEPSCs), IL-6 reduced the frequency of spontaneous IPSCs (sIPSCs). Notably, IL-1beta both enhanced the frequency and amplitude of sEPSCs and reduced the frequency and amplitude of sIPSCs. Consistently, TNFalpha and IL-1beta enhanced AMPA- or NMDA-induced currents, and IL-1beta and IL-6 suppressed GABA- and glycine-induced currents. Furthermore, all the PICs increased cAMP response element-binding protein (CREB) phosphorylation in superficial dorsal horn neurons and produced heat hyperalgesia after spinal injection. Surprisingly, soluble IL-6 receptor (sIL-6R) produced initial decrease of sEPSCs, followed by increase of sEPSCs and CREB phosphorylation. Spinal injection of sIL-6R also induced heat hyperalgesia that was potentiated by coadministration with IL-6. Together, our data have demonstrated that PICs induce central sensitization and hyperalgesia via distinct and overlapping synaptic mechanisms in superficial dorsal horn neurons either by increasing excitatory synaptic transmission or by decreasing inhibitory synaptic transmission. PICs may further induce long-term synaptic plasticity through CREB-mediated gene transcription. Blockade of PIC signaling could be an effective way to suppress

  4. Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Lopes, Carlos [Universidade do Vale do Paraiba, Centro de Oncologia Radioterapica do Vale do Paraiba, Universidade do Vale do Paraiba Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Callera, Fernando, E-mail: fcallera@gmail.com [Centro de Hematologia Onco-hematologia e Transplantes de Medula Ossea do Vale do Paraiba, Sao Paulo (Brazil)

    2012-03-15

    Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

  5. Tumour necrosis factor alpha (TNF-α) genetic polymorphisms and ...

    Indian Academy of Sciences (India)

    2Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University,. Nanning, Guangxi 530021, People's Republic of China. Abstract. Epidemiological studies have evaluated the association between tumour necrosis factor alpha (TNF-α)-308G/A and (TNF-α)-. 238G/A ...

  6. Tumour necrosis factor-alpha gene polymorphisms in Iranian ...

    African Journals Online (AJOL)

    ... progressive inflammatory destructive process of the bile ducts. This study evaluated the relationship between single-nucleotide polymorphisms in the promoter region of tumour necrosis factor-alpha (TNF-α) gene and bilaiary atresia. Materials and Methods: Genomic deoxyribonucleic acid from 16 patients with established ...

  7. Tumour necrosis factor alpha and interleukin 10 gene ...

    Indian Academy of Sciences (India)

    Tumour necrosis factor alpha and interleukin 10 gene polymorphisms and the risk of ischemic stroke in south Indian population. Shehnaz Sultana Venkata K. Kolla Yasovanthi Jeedigunta Pranay K. Penagaluru Sindhu Joshi P. Usha Rani P. P. Reddy. Research Note Volume 90 Issue 2 August 2011 pp 361-364 ...

  8. Interleukin-6 and tumor necrosis factor-alpha gene polymorphisms in chronic idiopathic urticaria.

    Science.gov (United States)

    Tavakol, M; Amirzargar, A A; Movahedi, M; Aryan, Z; Bidoki, A Z; Gharagozlou, M; Aghamohammadi, A; Nabavi, M; Ahmadvand, A; Behniafard, N; Heidari, K; Soltani, S; Rezaei, N

    2014-01-01

    This study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU). Ninety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C -174, G/A nt565) and TNF-α (G/A -308, G/A -238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group. G allele was significantly higher in the patients at locus of -238 of promoter of TNF-α gene (p<0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at -308 and GA at -238 of TNF-α gene (p<0.05 and p<0.001, respectively), CG at -174 and GG at +565 of IL-6 gene (p<0.05). Additionally, following genotypes were more common among patients with CIU: GG at -308 and -238 of TNF-α gene (p<0.05 and p<0.001, respectively), GG at -174 and GA at +565 of IL-6 gene (p<0.05). Pro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  9. Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

    Science.gov (United States)

    Bahia, Malkeet S; Silakari, Om

    2010-05-01

    Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

  10. Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

    Directory of Open Access Journals (Sweden)

    Weibo Cai Ph.D.

    2008-01-01

    Full Text Available Tumor necrosis factor-alpha (TNF-α, a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.

  11. Kinetics of intraocular tumor necrosis factor and interleukin-6 in endotoxin-induced uveitis in the rat

    NARCIS (Netherlands)

    de Vos, A. F.; van Haren, M. A.; Verhagen, C.; Hoekzema, R.; Kijlstra, A.

    1994-01-01

    To determine the kinetics of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in serum and aqueous humor of rats with different susceptibilities to endotoxin-induced uveitis (EIU), after footpad injection of lipopolysaccharide (LPS). Samples were collected from EIU-susceptible Lewis rats and

  12. Tumour necrosis factor-induced uveitis in the Lewis rat is associated with intraocular interleukin 6 production

    NARCIS (Netherlands)

    de Vos, A. F.; van Haren, M. A.; Verhagen, C.; Hoekzema, R.; Kijlstra, A.

    1995-01-01

    Lewis rats were injected with recombinant murine tumour necrosis factor-alpha either intravitreally (0.08-50 ng) or intracardially (1 microgram). The intraocular inflammatory response induced by tumour necrosis factor was examined by slit-lamp and protein extravasation into aqueous humor was

  13. Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Toledo JO

    2015-01-01

    Full Text Available Juliana O Toledo,1 Clayton F Moraes,2,3 Vinícius C Souza,2 Audrey C Tonet-Furioso,2 Luís CC Afonso,4 Cláudio Córdova,3 Otávio T Nóbrega1,2 1Graduate Program in Health Sciences, 2Graduate Program in Medical Sciences, University of Brasília, Brasília, 3Graduate Program in Gerontology, Catholic University of Brasília, Brasília, 4Research Center in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ] in response to multivariate drug directions for blood pressure (BP control.Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention.Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01 at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group.Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in

  14. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Dominguez, Helena; Storgaard, Heidi; Rask-Madsen, Christian

    2005-01-01

    OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha blockade with etanercept could reverse vascular and metabolic...... insulin resistance. METHOD AND RESULTS: Twenty obese patients with type 2 diabetes were randomized to etanercept treatment (25 mg subcutaneously twice weekly for 4 weeks) or used as controls in an open parallel study. Forearm blood flow and glucose uptake were measured during intra-arterial infusions...... of serotonin, sodium nitroprusside and insulin co-infused with serotonin. Beta-cell function was assessed with oral and intra-venous glucose tolerance tests and whole-body insulin sensitivity by hyperinsulinemic euglycemic clamps. Plasma levels of C-reactive protein and interleukin-6 decreased significantly...

  15. Correlation Between Tumor Necrosis Factor Alpha and Proteinuria ...

    African Journals Online (AJOL)

    Serum tumor necrosis factor-α (TNF-α), urine TNF-α and C-reactive protein (CRP) levels were measured in all subjects. Correlations between these inflammatory parameters and degree of proteinuria, duration of diabetes and degree of glycemic control were examined. Results: Levels of the three inflammatory parameters ...

  16. Glaucomatous neurodegeneration: An eye on tumor necrosis factor-alpha

    OpenAIRE

    Renu Agarwal; Puneet Agarwal

    2012-01-01

    Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expressi...

  17. Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo

    DEFF Research Database (Denmark)

    Hansen, P R; Svendsen, Jesper Hastrup; Høyer, S

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis of tissue injury, and high circulating levels of TNF-alpha are found in a variety of pathological conditions. In open-chest anesthetized dogs, the effects of intracoronary recombinant human TNF-alpha (rTNF-alpha; 100...

  18. Effect of tumor necrosis factor-alpha infusion on the incretin effect in healthy volunteers

    DEFF Research Database (Denmark)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumor necrosis factor-alpha (TNF-α). Whereas TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce...

  19. Passive immunization against tumor necrosis factor-alpha impairs host defense during pneumococcal pneumonia in mice

    NARCIS (Netherlands)

    van der Poll, T.; Keogh, C. V.; Buurman, W. A.; Lowry, S. F.

    1997-01-01

    Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. We sought to determine the role of tumor necrosis factor-alpha (TNF) in the pathogenesis of pneumococcal pneumonia. Induction of pneumonia in C57B1/6 mice by intranasal inoculation with 10(6) colony-forming units

  20. New Method of Inhibition of Activity of Tumor Necrosis Factor Alpha In Patients with Psoriasis.

    Science.gov (United States)

    Gerasun, Borys A

    2016-01-01

    A new method of reduction of tumor necrosis factor alpha activity via intradermal immunization with inactivated autoleukocytes (patent UA97493 (2015) [1]) has been presented in the article. New patents from various countries have been analyzed [2-7]. Patients with psoriasis (24) with high level of tumor necrosis factor alpha in their blood (. 30pg/ml) were immunized with autoleukocytes. Leukocytes were isolated by centrifuging plasma, obtained after precipitation of a patient's heparinized peripheral venous blood. Precipitate was suspended in 1.0 - 1.5ml of a patient's blood serum and 0.1ml of blood was injected into the skin of the back. For determination of autoleukocyte immunization efficacy, concentration of tumor necrosis factor alpha in a patient's blood was compared prior to immunization and at different periods after immunization. In 30 days after single immunization, a considerable decrease in cytokine concentration was observed in all patients (100%); it reduced to zero in 16 out of 24 of immunized individuals (66.7%). The degree of reduction and duration of the achieved effect were individual, thus, if necessary the immunization was repeated several times. The procedure was well tolerated, and general condition of patients was improved. The method of reduction of tumor necrosis factor alpha activity is recommended for implementation into clinical practice.

  1. Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis.

    NARCIS (Netherlands)

    Radovits, B.J.; Kievit, W.; Fransen, J.; Laar, M.A. van der; Jansen, T.L.Th.A.; Riel, P.L.C.M. van; Laan, R.F.J.M.

    2009-01-01

    OBJECTIVE: To investigate the influence of age on the effectiveness and tolerance of antitumour necrosis factor alpha (TNFalpha) therapy in rheumatoid arthritis (RA). METHODS: 730 patients of the Dutch Rheumatoid Arthritis Monitoring (DREAM) register were categorised into three groups according to

  2. Increased voluntary exercise in mice deficient for tumour necrosis factor-alpha and lymphotoxin-alpha.

    NARCIS (Netherlands)

    Netea, M.G.; Kullberg, B.J.; Vonk, A.G.; Verschueren, I.; Joosten, L.A.B.; Meer, J.W.M. van der

    2007-01-01

    BACKGROUND: The endogenous mediators playing a role in the sensing of fatigue and cessation of exercise are yet to be characterized. We hypothesized that proinflammatory cytokines, in particular tumour necrosis factor-alpha (TNFalpha) and lymphotoxin-alpha (LT) transmit signals leading to fatigue.

  3. The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa Abdul-Hussein H; Krag, Aleksander; Olaison, Gunnar

    2013-01-01

    Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.......Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications....

  4. Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

    Science.gov (United States)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke; Solomon, Thomas P J; Lehrskov-Schmidt, Lars; Holst, Jens Juul; Møller, Kirsten

    2013-11-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Serum levels of interleukin-6, tumor necrosis factor-alpha and interferon-gama in infants with and without dengue

    OpenAIRE

    Restrepo,Berta Nelly; Isaza,Diana María; Salazar,Clara Lina; Ramírez,Ruth; Ospina,Marta; Alvarez,Luis Gonzalo

    2008-01-01

    This study compared the serum levels of IL-6, TNF-alpha and IFN-gamma, in children under 1 year of age with and without dengue. Sera were collected from a total of 41 children living in the Department of Antioquia, Colombia (27 patients with dengue and 14 controls). The results showed higher cytokine levels in children with dengue than without dengue, with statistically significant differences for IL-6 and IFN-gamma. No statistically significant differences were found between clinical forms, ...

  6. Interleukin-17 induces hyperresponsive interleukin-8 and interleukin-6 production to tumor necrosis factor-alpha in structural lung cells

    NARCIS (Netherlands)

    van den Berg, Arjen; Kuiper, Mathys; Snoek, Mieke; Timens, Wim; Postma, Dirkje S.; Jansen, Henk M.; Lutter, René

    2005-01-01

    Lung epithelial cells contribute to local inflammation by the production of pro-inflammatory mediators like interleukin (IL)-8 and IL-6. Although their production depends on gene transcription, previous studies showed that post-transcriptional mechanisms modulate IL-8 and IL-6 production. Human lung

  7. Tumor necrosis factor-alpha is a potential diagnostic biomarker for chronic neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Xu, Jun; E, Xiaoqiang; Liu, Huiyong; Li, Feng; Cao, Yanhui; Tian, Jun; Yan, Jinglong

    2015-05-19

    Neuropathic pain (NP) is one of the most common complications after spinal cord injury (SCI), but no protein biomarkers has ever been introduced into clinical diagnosis. Previous studies implicated that toll-like receptor (TLR) 4 played a critical role in the development of NP in animal SCI models. Here, a total of 140 participants were recruited, 70 of them were SCI-NP subject and the rest 70 controls did not show neuropathic symptoms. TLR4 was upregulated significantly in SCI-NP patients compared with SCI-noNP subjects. Furthermore, we measured the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), two TLR4 downstream pro-inflammatory cytokines, to assess their diagnostic values. Receiver operating characteristics (ROC) analysis revealed that TNF-α had great potential advantages to predict the progression of neuropathy, the risks of NP were strongly increased in SCI subjects with higher levels of TNF-α (odds ratio: 4.92; 95% confidence interval: 1.89-12.32). These results suggested neuro-immune activation contributed to the development of neuropathic disorder after SCI, and TNF-α could be a potential sensitive diagnostic biomarker for chronic neuropathic pain in SCI patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Inhibitory effect of nicotinamide on in vitro and in vivo production of tumor necrosis factor-alpha.

    Science.gov (United States)

    Fukuzawa, M; Satoh, J; Muto, G; Muto, Y; Nishimura, S; Miyaguchi, S; Qiang, X L; Toyota, T

    1997-10-01

    Nicotinamide, a pellagra-preventive factor, has multiple functions such as inhibition of poly-ADP-ribose synthetase, inhibition of inducible nitric oxide synthase, free radical scavenging and suppression of major histocompatibility complex class II expression and ICAM-1 expression on endothelial cells. In addition to these, we have found an inhibitory effect of nicotinamide on production of tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo. Lipopolysaccharide (LPS)-induced in vitro TNF-alpha production by human peripheral blood mononuclear cells, measured by enzyme-linked immunosorbent assay (ELISA), was significantly inhibited with more than 1 x 10(-3) mol/l of nicotinamide, while interleukin-1-beta was not inhibited and interleukin-6 was slightly inhibited even with 10(-2) mol/l. Oral administration of nicotinamide with more than 62.5 mg/kg also significantly inhibited LPS-induced serum TNF-alpha production measured by ELISA and bioassay in Balb/c mice. Thus, nicotinamide has an inhibitory effect on TNF-alpha production that may be beneficial to TNF-alpha-mediated diseases.

  9. Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors

    OpenAIRE

    1991-01-01

    Histamine and tumor necrosis factor alpha (TNF-alpha) can each contribute to the pathogenesis of allergic reactions and chronic inflammatory diseases. We now report the effect of histamine on gene expression and total cellular synthesis of TNF-alpha. Lipopolysaccharide (LPS)-induced synthesis of TNF-alpha in peripheral blood mononuclear cells (PBMC) from 18 healthy donors was suppressed by histamine concentrations from 10(-6) to 10(-4) M, levels comparable with those measured in tissues after...

  10. Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells

    NARCIS (Netherlands)

    Endres, S; Fülle, H J; Sinha, B; Stoll, D; Dinarello, C A; Gerzer, R; Weber, P.C.

    Recent reports have shown that phosphodiesterase (PDE) inhibitors suppress production of tumour necrosis factor-alpha (TNF-alpha) in mouse macrophages. In the present study we show that theophylline, pentoxifylline and 3-isobutyl-1-methylxanthine markedly suppress the lipopolysaccharide

  11. High Serum Interleukin-10 and Tumor Necrosis Factor Alpha Levels in Chronic Paracoccidioidomycosis

    Science.gov (United States)

    Fornari, M. C.; Bava, A. J.; Guereño, M. T.; Berardi, V. E.; Silaf, M. R.; Negroni, R.; Diez, R. A.

    2001-01-01

    In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean ± standard error of the mean), were higher than in normal controls (n = 8): 186 ± 40 versus 40 ± 7 (P < 0.05), 203 ± 95 versus 20 ± 8 (P = 0.001), and 96.3 ± 78.57 versus 1.19 ± 1.19 (P = 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls. PMID:11527826

  12. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OHD concentrations in healthy women

    Directory of Open Access Journals (Sweden)

    Heffernan Mary E

    2008-07-01

    Full Text Available Abstract Background Circulating 25 hydroxyvitamin D (25 (OHD, an accurate measure of vitamin D status, is markedly greater in individuals with increased exposure to ultraviolet B (UVB light via sunlight or the use of artificial UV light. Aside from the known relationship between vitamin D and bone, vitamin D has also been implicated in immune function and inflammation. Furthermore, a mass of evidence is accumulating that vitamin D deficiency could lead to immune malfunction. Our overall objective was to study the relationship between vitamin D status (as determined by serum 25(OH D concentrations and inflammatory markers in healthy women. Methods This observational study included 69 healthy women, age 25–82 years. Women with high UVB exposure and women with minimal UVB exposure were specifically recruited to obtain a wide-range of serum 25(OHD concentrations. Health, sun exposure and habitual dietary intake information were obtained from all subjects. Body composition was determined by dual-energy-x-ray absorptiometry. A fasting blood sample was collected in the morning and analyzed for serum 25(OHD, parathyroid hormone (iPTH, estradiol (E2, cortisol, and inflammatory markers [tumor necrosis factor -alpha (TNF-α, interleukin-6 and -10 (IL-6, IL-10, and C-reactive protein (CRP]. Results Women with regular UVB exposure (Hi-D had serum 25(OHD concentrations that were significantly higher (p p Conclusion Serum 25(OHD status is inversely related to TNF-α concentrations in healthy women, which may in part explain this vitamin's role in the prevention and treatment of inflammatory diseases. Results gleaned from this investigation also support the need to re-examine the biological basis for determining optimal vitamin D status.

  13. Interleukin-10 and tumour necrosis factor-alpha serum levels in chronic Chagas disease patients.

    Science.gov (United States)

    Vasconcelos, R H T; Azevedo, E de A N; Diniz, G T N; Cavalcanti, M da G A de M; de Oliveira, W; de Morais, C N L; Gomes, Y de M

    2015-07-01

    In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease. © 2015 John Wiley & Sons Ltd.

  14. The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease: a systematic review.

    Science.gov (United States)

    El-Hussuna, Alaa; Krag, Aleksander; Olaison, Gunnar; Bendtsen, Flemming; Gluud, Lise L

    2013-12-01

    Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications. We assessed the effect of anti-tumor necrosis factor alpha on postoperative complications in patients with Crohn's disease undergoing abdominal surgery. Studies were identified through electronic and manual searches. Observational studies on patients with Crohn's disease undergoing laparoscopic or open abdominal surgery were included. Anti-tumor necrosis factor alpha agents were administered within 3 months before surgery. The primary outcome was anastomotic complications including overt dehiscence, intra-abdominal abscess, and enteric fistulas. Fourteen studies on 679 patients in the intervention (anti-tumor necrosis factor alpha) group and 2363 controls were included. Random-effects meta-analysis found no difference in anastomotic complications between the 2 groups (7.6% versus 8.2%; risk ratio, 0.91; 95% CI, 0.56-1.48). There was clear heterogeneity between studies. In subgroup analyses, the anti-tumor necrosis factor alpha increased anastomotic complications in trials with a lower risk of bias, but not in the studies with a higher bias risk (risk ratio, 1.63; 95% CI, 1.03-2.60 and risk ratio, 0.17; 95% CI, 0.05-0.60). In the overall analysis and in studies with a lower bias risk, anti-tumor necrosis factor alpha agents increased the risk of nonanastomotic surgical complications, major medical complications, and minor medical complications. Limitations of observations studies. In studies with a low risk of bias, anti-tumor necrosis factor alpha agents increased the risk of anastomotic complications. Inadequate bias control may lead to an underestimated risk of anastomotic complications.

  15. Influence of βS-globin haplotypes and hydroxyurea on tumor necrosis factor-alpha levels in sickle cell anemia.

    Science.gov (United States)

    Laurentino, Marília Rocha; Maia, Pedro Aurio; Barbosa, Maritza Cavalcante; Bandeira, Izabel Cristina Justino; Rocha, Lilianne Brito da Silva; Gonçalves, Romelia Pinheiro

    2014-03-01

    Sickle cell anemia is a chronic inflammatory disease characterized by an increased production of proinflammatory cytokines including tumor necrosis factor-alpha. Hydroxyurea, by decreasing the polymerization of hemoglobin, reduces inflammatory states. The effect of the genetic polymorphisms of sickle cell patients on tumor necrosis factor-alpha levels remains unknown. The aim of this study was to investigate the association of tumor necrosis factor-alpha levels with β-globin haplotypes and the use of hydroxyurea. A cross-sectional study was performed of 67 patients with sickle cell anemia diagnosed at steady-state in a referral hospital in Fortaleza, Ceará, Brazil. A group of 26 healthy individuals was used as control. βS-haplotype analysis was performed by restriction fragment length polymorphism-polymerase chain reaction. The tumor necrosis factor-alpha levels were measured by the enzyme-linked immunosorbent assay test. Laboratory data (complete blood count and fetal hemoglobin) and information regarding the use of hydroxyurea were obtained from medical records. Statistical analysis was performed using R software with the Kruskal-Wallis and Mann-Whitney tests. Statistical significance was established for p-values sickle cell anemia had significantly higher tumor necrosis factor-alpha levels than controls (p-values sickle cell anemia patients who were receiving hydroxyurea treatment than those who were not (p-value = 0.1249). Sickle cell anemia patients with Bantu/n genotype had significantly higher levels than patients with the Bantu/Benin genotype (p-value = 0.0021). In summary, βS-globin haplotypes, but not hydroxyurea therapy, have a role in modulating tumor necrosis factor-alpha levels in sickle cell anemia adults at steady-state. Many previous studies have investigated prognosis and inflammatory states in sickle cell anemia patients, but the discovery that tumor necrosis factor-alpha levels vary according to the genetic polymorphism of the patient is a

  16. [Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

    Science.gov (United States)

    Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

    2014-11-18

    To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

  17. Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus-infected cells to heat and radiation

    International Nuclear Information System (INIS)

    Wong, G.H.; McHugh, T.; Weber, R.; Goeddel, D.V.

    1991-01-01

    We report here that infection of the human T-cell line HUT-78 with human immunodeficiency virus (HIV) increases its sensitivity to heat and radiation toxicity. A possible explanation for this result may be the reduced expression of manganous superoxide dismutase (MnSOD) in HIV-infected cells compared to uninfected cells. Tumor necrosis factor alpha (TNF-alpha) further sensitizes HIV-infected cells but not uninfected cells to heat and radiation. This is consistent with the ability of TNF-alpha to induce the expression of MnSOD in uninfected but not in HIV-infected cells. HIV-infected HUT-78 cell lines engineered to overexpress MnSOD are more resistant to heat and radiation than HIV-infected cells that do not overexpress MnSOD. However, treatment with TNF-alpha still sensitizes these cells to heat and radiation

  18. Biodentine Reduces Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells.

    Science.gov (United States)

    El Karim, Ikhlas A; McCrudden, Maelíosa T C; McGahon, Mary K; Curtis, Tim M; Jeanneau, Charlotte; Giraud, Thomas; Irwin, Chris R; Linden, Gerard J; Lundy, Fionnuala T; About, Imad

    2016-04-01

    The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. Immunofluorescent staining revealed TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha-induced TRPA1 responses after Biodentine treatment. In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  19. Serum tumour necrosis factor alpha in osteopenic and osteoporotic postmenopausal females: A cross-sectional study in Pakistan.

    Science.gov (United States)

    Murad, Rafat; Shezad, Zahra; Ahmed, Saara; Ashraf, Mussarat; Qadir, Murad; Rehman, Rehana

    2018-03-01

    To compare biochemical parameters serum tumour necrosis factor alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D in postmenopausal women. This cross-sectional study was carried out from June 2015 to July 2016 at Jinnah Medical and Dental College, Karachi, and comprised postmenopausal women. Bone mineral density done by dual energy X-ray absorptiometryscan categorised subjects by World Health Organisation classification into normal (T score > -1) osteopenic (T score between -1 and -2.5) and osteoporotic (T score osteoporotic. There was significant difference in mean body mass index, serum tumour necrosis factor alpha and calcium in all the three groups (posteoporotic group (posteoporotic groups (p>0.05). A significant difference was observed for mean tumour necrosis factor alpha values between normal and osteoporotic groups (posteoporotic groups (p>0.05). Increased bone turnover in postmenopausal osteopenic women can be predicted by increased serum cytokine.

  20. Influence of ?S-globin haplotypes and hydroxyurea on tumor necrosis factor-alpha levels in sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Marília Rocha Laurentino

    2014-04-01

    Full Text Available Background: Sickle cell anemia is a chronic inflammatory disease characterized by an increased production of proinflammatory cytokines including tumor necrosis factor-alpha. Hydroxyurea, by decreasing the polymerization of hemoglobin, reduces inflammatory states. The effect of the genetic polymorphisms of sickle cell patients on tumor necrosis factor-alpha levels remains unknown. Objective: The aim of this study was to investigate the association of tumor necrosis factor-alpha levels with β-globin haplotypes and the use of hydroxyurea. Methods: A cross-sectional study was performed of 67 patients with sickle cell anemia diagnosed at steady-state in a referral hospital in Fortaleza, Ceará, Brazil. A group of 26 healthy individuals was used as control. βS-haplotype analysis was performed by restriction fragment length polymorphism-polymerase chain reaction. The tumor necrosis factor-alpha levels were measured by the enzyme-linked immunosorbent assay test. Laboratory data (complete blood count and fetal hemoglobin and information regarding the use of hydroxyurea were obtained from medical records. Statistical analysis was performed using R software with the Kruskal-Wallis and Mann-Whitney tests. Statistical significance was established for p-values < 0.05 for all analyses. Results: The mean age of the participants was 35.48 years. Patients with sickle cell anemia had significantly higher tumor necrosis factor-alpha levels than controls (p-values < 0.0001. Tumor necrosis factor-alpha levels were lower in sickle cell anemia patients who were receiving hydroxyurea treatment than those who were not (p-value = 0.1249. Sickle cell anemia patients with Bantu/n genotype had significantly higher levels than patients with the Bantu/Benin genotype (p-value = 0.0021. Conclusion: In summary, βS-globin haplotypes, but not hydroxyurea therapy, have a role in modulating tumor necrosis factor-alpha levels in sickle cell anemia adults at steady-state. Many

  1. Tipping the balance: anti-tumour necrosis factor alpha therapy may damage cerebral nerve reservation.

    Science.gov (United States)

    Lin, Yun; Zou, Qinghua; Li, Haitao

    2009-12-01

    Anti-tumour necrosis factor alpha therapy has transformed the treatment of certain inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease and ankylosing spondylitis, but onset of demyelinating events associated with multiple sclerosis as an adverse event was continuously reported, and such adverse events were only viewed as occasional. Multiple sclerosis is an autoimmune demyelinating disorder affecting central nervous system, with varied clinical manifestations of cognitive, visual and motor network disorder. Recently, there is increasing evidence from functional magnetic resonance that cortical reorganization, a property that allows the central nervous system to adapt itself to various brain insults, which was viewed as to limit the clinical expression of tissue damage in patients with multiple sclerosis. In light of the mentioned above, we hypothesis that cerebral tissue damage may existed in a broader aspects of patients treated with anti-tumour necrosis factor therapy, but its clinical manifestations from brain lesions were compensated by cortical reorganization. In other words, cerebral nerve reservation may be damaged by the therapy. If confirmed, the hypothesis may lead to a safety concern of the therapy, and an insight of the pathophysiology of both multiple sclerosis and certain inflammatory diseases.

  2. Tumour necrosis factor-alpha (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Jónasdóttir, O; Petersen, J; Bendtzen, K

    2001-01-01

    Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor alpha (TNFalpha) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFa are mediated by TNF receptors (TNF...

  3. Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients

    NARCIS (Netherlands)

    Feelders, R. A.; Swaak, A. J.; Romijn, J. A.; Eggermont, A. M.; Tielens, E. T.; Vreugdenhil, G.; Endert, E.; van Eijk, H. G.; Berghout, A.

    1999-01-01

    Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects

  4. Lipopolysaccharide induces expression of tumour necrosis factor alpha in rat brain : inhibition by methylprednisolone and by rolipram

    NARCIS (Netherlands)

    Buttini, M; Mir, A; Appel, K; Wiederhold, KH; Limonta, S; GebickeHaerter, PJ; Boddeke, HWGM

    1997-01-01

    1 We have investigated the effects of the phosphodiesterase (PDE) type TV inhibitor rolipram and of the glucocorticoid methylprednisolone on the induction of tumour necrosis factor alpha (TNF-alpha) mRNA and protein in brains of rats after peripheral administration of lipopolysaccharide (LPS). 2

  5. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

    Science.gov (United States)

    Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

  6. Inhibition of tumor necrosis factor-alpha with anti-diabetic agents.

    Science.gov (United States)

    Fukuzawa, M; Satoh, J; Qiang, X; Miyaguchi, S; Sakata, Y; Nakazawa, T; Ikehata, F; Ohta, S; Toyota, T

    1999-03-01

    It has recently been indicated that tumor necrosis factor-alpha (TNF-alpha) production is increased under chronic hyperglycemia and TNF-alpha has harmful effects on insulin sensitivity and possibly on chronic diabetic complications. Therefore it will be favorable for diabetes treatment if anti-diabetic agents also have anti-TNF-alpha activities. In this study, we have investigated effects of hypoglycemic sulfonylureas (gliclazide and glibenclamide) and a thiazolidinedione (troglitazone) on lipopolysaccharide-induced TNF-alpha production, which was evaluated by immunoassay and bioassay, in vivo using mice and partly in vitro using human peripheral blood mononuclear cells. Gliclazide significantly inhibited TNF-alpha production in vivo and also in vitro at a concentration of 10(-3) mol/l. However, glibenclamide had neither effect on TNF-alpha production nor action. On the other hand, troglitazone inhibited action rather than production of TNF-alpha in vivo. In vitro troglitazone (10(-4) mol/l) significantly reduced cytolytic activity of TNF-alpha against LM cells. These results indicate that gliclazide and troglitazone have inhibitory effect on TNF-alpha.

  7. Modulation of tumor necrosis factor-alpha production with anti-hypertensive drugs.

    Science.gov (United States)

    Fukuzawa, M; Satoh, J; Ohta, S; Takahashi, K; Miyaguchi, S; Qiang, X; Sakata, Y; Nakazawa, T; Takizawa, Y; Toyota, T

    2000-06-01

    It is well known that some anti-hypertensive drugs affect insulin sensitivity and that tumor necrosis factor-alpha (TNF-alpha) is a mediator of obesity-associated insulin resistance. In this study, we have investigated the effect of anti-hypertensive drugs, calcium (Ca) channel blockers (amlodipine, manidipine and nicardipine), an alpha(1)-blocker (doxazosin), a beta(1)-blocker (metoprolol), and a thiazide diuretic (hydrochlorothiazide), on lipopolysaccharide (LPS)-induced TNF-alpha production. TNF-alpha production, measured with a bioassay and an immunoassay, was evaluated both in vivo and in vitro, by utilizing mice and a human peripheral blood mononuclear cell culture, respectively. Nicardipine, or amlodipine, manidipine and doxazosin significantly inhibited TNF-alpha production in mice at doses more than one or ten times higher than those used clinically, respectively. On the other hand, metoprolol increased TNF-alpha production at doses of more than 10 times those used clinically, whereas hydrochlorothiazide did not alter production of the cytokine. The in vivo effects of these drugs were not necessary parallel to the in vitro effects. Because high doses of these drugs in mice correspond to clinical doses and effects in human, these actions may be related to beneficial and/or harmful effects of these drugs on TNF-alpha mediated diseases, including insulin resistance.

  8. Analysis of Relationship between Tumor Necrosis Factor Alpha Gene (G308A Polymorphism) with Preterm Labor.

    Science.gov (United States)

    Jafarzadeh, Lobat; Danesh, Azar; Sadeghi, Marzieh; Heybati, Fateme; Hashemzadeh, Morteza

    2013-08-01

    Increased concentrations of tumor necrosis factor alpha (TNF-α) in blood and amniotic fluid are observed in women with preterm delivery (PTD) and TNF-α mutations at -308 position are associated with higher expression of this gene. Therefore, we compared the frequency of G308A transition in the promoter region of TNF-α gene of women and neonates delivered preterm with the normal subjects. This cross-sectional study was performed on 135 mothers who were referred for delivery. According to the gestational age, mothers and their neonates were allocated to the case (preterm, 64 subjects) and control (term, 71 subjects) groups. Using the polymerase chain reaction, restrictive fragment length polymorphism (RFLP), genotyping was performed on both maternal peripheral blood and cord blood samples to determine single nucleotide polymorphism in the promoter region of TNF-α gene at -308. Two mothers in the case group, one mother in the control group and one neonate in the case group had genotyping assays (GA) mutation. All other subjects had normal GG genotype. Frequency of GA mutation was not significantly different between two groups (P = 0.47). There is no significant association between PTD and either maternal or fetal TNF-α -308 polymorphism and frequency ofGAmutation is not significantly increased in mothers and neonates delivered preterm. It means that the presence of this mutation by itself does not modify the overall risk of PTD. Investigations on the combination of various polymorphisms indifferent genes are recommended to achieve more accurate results.

  9. The Role of Tumor Necrosis Factor- alpha and Resistin in Nonalcoholic Fatty Liver Disease

    International Nuclear Information System (INIS)

    Alkady, M.M.

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents one of the most common liver diseases. It is strongly associated with obesity and insulin resistance and is thought to be a part of the metabolic syndrome. It can progress from simple fatty liver to steatohepatitis, cirrhosis and liver failure. Adipocytokines, synthesized in adipose tissue, are involved in the pathophysiology of many acute and chronic liver diseases. The aim of this study was to investigate the role of Tumor Necrosis Factor-alpha (TNF-alpha) and resistin in the pathogenesis of NAFLD and their correlation to the severity of the disease. Serum concentration of TNF-alpha and resistin were measured in 20 patients with NAFLD and 20 healthy controls with ELISA method. The results of this study revealed that serum levels of both adipokines were significantly elevated in NAFLD patients than controls (P<0.01). Moreover, they were significantly higher in patients with nonalcoholic steatohepatitis than in patients with simple fatty liver. There was a significant positive correlation between TNF-alpha, resistin and each of AST, ALT and HOMA. Similarly, the results showed a significant positive correlation between the two studied adipokines, TNF-alpha and resistin (P<0.001). We conclude that TNF-alpha and resistin have a role in the pathogenesis of NAFLD and they may be promising markers for the progressin to steatohepatitis and inhibition of their activities by drugs may be a new approach for the treatment of NAFLD

  10. Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells.

    Science.gov (United States)

    Cui, W; Li, L X; Sun, C M; Wen, Y; Zhou, Y; Dong, Y L; Liu, P

    2010-04-01

    The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-alpha) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell microporous filters and treated with TNF-alpha (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-alpha treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-alpha decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-alpha did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-alpha increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

  11. Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    W. Cui

    2010-04-01

    Full Text Available The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

  12. Thermotherapy-induced reduction in glioma invasiveness is mediated by tumor necrosis factor-alpha.

    Science.gov (United States)

    Qin, L J; Zhang, T; Jia, Y S; Zhang, Y B; Zhang, Y X; Wang, H T

    2015-10-02

    Thermotherapy has been proven to be effective for the treatment of various tumors, including glioma. We determined whether tumor necrosis factor-alpha (TNF-α) is involved in the regulation of the biological processes of glioma development. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were used to investigate the levels of TNF-α mRNA and heat shock factor-1 (HSF1) protein, respectively, in glioma cells. Radioimmunoassay was used to dynamically monitor the contents of TNF-α in the nutrient fluid of C6 cells after thermotherapy treatment. Crystal violet staining was used to determine glioma invasiveness. The most obvious increases in HSF1 protein and TNF-α mRNA in C6 cells were observed at 30 and 60 min after thermotherapy, respectively. In addition, the radioactivity of TNF-α in the culture fluid of the C6 cells reached a peak after 120 min of thermotherapy. In addition, glioma invasiveness decreased and the concentration of TNF-α reached a maximum after 120 min of thermotherapy. Our results show that the decrease in thermotherapy-mediated glioma invasiveness is due to the accelerated release of TNF-α, which could promote the release of HSF1 from neurospongioma cells.

  13. Tumor necrosis factor alpha maintains denervation-induced homeostatic synaptic plasticity of mouse dentate granule cells

    Directory of Open Access Journals (Sweden)

    Denise eBecker

    2013-12-01

    Full Text Available Neurons which lose part of their input respond with a compensatory increase in excitatory synaptic strength. This observation is of particular interest in the context of neurological diseases, which are accompanied by the loss of neurons and subsequent denervation of connected brain regions. However, while the cellular and molecular mechanisms of pharmacologically induced homeostatic synaptic plasticity have been identified to a certain degree, denervation-induced homeostatic synaptic plasticity remains not well understood. Here, we employed the entorhinal denervation in vitro model to study the role of tumor necrosis factor alpha (TNFα on changes in excitatory synaptic strength of mouse dentate granule cells following partial deafferentation. Our experiments disclose that TNFα is required for the maintenance of a compensatory increase in excitatory synaptic strength at 3/4 days postlesion (dpl, but not for the induction of synaptic scaling at 1 - 2 dpl. Furthermore, laser capture microdissection (LMD combined with quantitative PCR (qPCR demonstrates an increase in TNFα-mRNA levels in the denervated zone, which is consistent with our previous finding on a local, i.e., layer-specific increase in excitatory synaptic strength at 3 - 4 dpl. Immunostainings for the glial fibrillary acidic protein (GFAP and TNFα suggest that astrocytes are a source of TNFα in our experimental setting. We conclude that TNFα-signaling is a major regulatory system that aims at maintaining the homeostatic synaptic response of denervated neurons.

  14. Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha.

    Science.gov (United States)

    Dharmani, Poonam; Strauss, Jaclyn; Ambrose, Christian; Allen-Vercoe, Emma; Chadee, Kris

    2011-07-01

    The etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial species Fusobacterium nucleatum is a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only live F. nucleatum induced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasive F. nucleatum isolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal that F. nucleatum may represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

  15. Genetically engineered bacteriophage delivers a tumor necrosis factor alpha antagonist coating on neural electrodes

    International Nuclear Information System (INIS)

    Kim, Young Jun; Nam, Chang-Hoon; Jin, Young-Hyun; Stieglitz, Thomas; Salieb-Beugelaar, Georgette B

    2014-01-01

    This paper reports a novel approach for the formation of anti-inflammatory surface coating on a neural electrode. The surface coating is realized using a recombinant f88 filamentous bacteriophage, which displays a short platinum binding motif and a tumor necrosis factor alpha antagonist (TNF-α antagonist) on p3 and p8 proteins, respectively. The recombinant bacteriophages are immobilized on the platinum surface by a simple dip coating process. The selective and stable immobilization of bacteriophages on a platinum electrode is confirmed by quartz crystal microbalance with dissipation monitoring, atomic force microscope and fluorescence microscope. From the in vitro cell viability test, the inflammatory cytokine (TNF-α) induced cell death was prevented by presenting recombinant bacteriophage coating, albeit with no significant cytotoxic effect. It is also observed that the bacteriophage coating does not have critical effects on the electrochemical properties such as impedance and charge storage capacities. Thus, this approach demonstrates a promising anti-apoptotic as well as anti-inflammatory surface coating for neural implant applications. (paper)

  16. Tumor necrosis factor alpha of teleosts: in silico characterization and homology modeling

    Directory of Open Access Journals (Sweden)

    Tran Ngoc Tuan

    2016-10-01

    Full Text Available Tumor necrosis factor alpha (TNF- is known to be crucial in many biological activities of organisms. In this study, physicochemical properties and modeling of TNF- protein of fish was analyzed using in silico approach. TNF- proteins selected from fish species, including grass carp (Ctenopharyngodon idella, zebra fish (Danio rerio, Nile tilapia (Oreochromis niloticus, goldfish (Carassius auratus, and rainbow trout (Oncorhynchus mykiss were used in this study. Physicochemical characteristics with molecular weight, theoretical isoelectric point, extinction coefficient, aliphatic index, instability index, total number of negatively charged residues and positively charged residues, and grand average of hydropathicity were computed. All proteins were classified as transmembrane proteins. The “transmembrane region” and “TNF” domain were identified from protein sequences. The function prediction of proteins was also performed. Alpha helices and random coils were dominating in the secondary structure of the proteins. Three-dimensional structures were predicted and verified as good structures for the investigation of TNF- of fish by online server validation.

  17. Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization to Infection

    Directory of Open Access Journals (Sweden)

    Nadia Belmellat

    2017-11-01

    Full Text Available Tumor necrosis factor-alpha (TNF-α blockade is an effective treatment for rheumatoid arthritis (RA and other inflammatory diseases, but in patients, it is associated with reduced resistance to the infectious agents Mycobacterium tuberculosis and Listeria monocytogenes, among others. Our goal was to model infection and arthritis in mice and to compare etanercept, a currently used anti-TNF-α inhibitor, to an anti-TNF-α vaccine. We developed a murine surrogate of the TNF-α kinoid and produced an anti-murine TNF-α vaccine (TNFKi composed of keyhole limpet hemocyanin conjugated to TNF-α, which resulted in anti-TNF-α antibody production in mice. We also used etanercept (a soluble receptor of TNF commonly used to treat RA as a control of TNF neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected against inflammation similar to etanercept. In a mouse model of acute L. monocytogenes infection, all TNFKi-treated mice showed cleared bacterial infection and survived, whereas etanercept-treated mice showed large liver granulomas and quickly died. Moreover, TNFKi mice infected with the virulent H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept-treated mice or controls. Depending on the TNF-α blockade strategy, treating arthritis with a TNF-α inhibitor could result in a different profile of infection suceptibility. Our TNFKi vaccine allowed for a better remaining host defense than did etanercept.

  18. Tumor Necrosis Factor-Alpha in Peripical Tissue Exudates of Teeth with Apical Periodontitis

    Directory of Open Access Journals (Sweden)

    Sonja Pezelj-Ribaric

    2007-01-01

    Full Text Available Aim. The aim of this study was to determine tumor necrosis factor-alpha (TNF-α levels in periapical exudates and to evaluate their relationship with radiological findings. Methodology. Periapical exudates were collected from root canals of 60 single-rooted teeth using absorbent paper points. TNF-α levels were determined by enzyme-linked immunosorbent assays. The samples were divided into three groups according to the periapical radiolucent area. Results. Nonparametric Kruskal-Wallis test revealed significant differences between TNF-α concentrations in control group (40, 57±28, 15 pg/mL and group with larger radiolucent areas (2365, 79±582, 95 pg/mL, as well as between control and canals with small radiolucent areas (507, 66±278, 97 (P<.05. Conclusions. The levels of TNF-α increase significantly in teeth with periapical pathosis, from smaller to bigger lesions. This research and its results have shown that objective analysis of the TNF-α levels enables establishment of a relationship between different concentrations of TNF-α and different radiological changes.

  19. Cytokine gene polymorphism (interleukin-1β +3954, Interleukin-6 [-597/-174] and tumor necrosis factor-α -308) in chronic periodontitis with and without type 2 diabetes mellitus.

    Science.gov (United States)

    Sharma, Nitin; Joseph, Rosamma; Arun, R; Chandni, R; Srinivas, K Lekshmy; Banerjee, Moinak

    2014-01-01

    Pro-inflammatory cytokine gene polymorphisms are potential candidates for susceptibility for both type 2 diabetes mellitus (DM) and chronic periodontitis (CHP). This study explored the association of interleukin-1 beta (IL-1 β) +3954, interleukin-6 (IL-6) -597/-174 and tumor necrosis factor-alpha (TNF-α) -308 single nucleotide polymorphisms in CHP with and without type 2 DM in Malayalam speaking subjects of Dravidian ethnicity. This case control study consisted of 51 chronic periodontitis with type 2 diabetes mellitus (CHPDM) and 51 CHP patients as cases and 51 healthy subjects as controls. Polymorphisms were identified by polymerase chain reaction amplification followed by restriction enzyme digestion and gel electrophoresis. IL-1 β (+3954) TT genotype and T allele were significantly associated with CHPDM group when compared with CHP (P = 0.001), whereas CC genotype and allele C was higher in CHP subjects (P = 0.001). For IL-6 (-597) frequency of genotype GA/AA (P = 0.04) and allele A (P = 0.01) was lower in CHPDM group, and for TNF-α -308 the frequency of genotype GA (P = 0.01) and allele A (P = 0.01) was higher in CHP subjects when compared with controls. In Malayalam speaking Dravidian population, IL-6 (-597) genotype GA/AA and allele A appears to be protective for CHP with type 2 DM. Allele C of IL-1 β +3954 and allele A of TNF-α -308 appears to be risk factors for CHP individuals.

  20. Dissociative symptoms reflect levels of tumor necrosis factor alpha in patients with unipolar depression

    Directory of Open Access Journals (Sweden)

    Bizik G

    2014-04-01

    Full Text Available Gustav Bizik,1 Petr Bob,1 Jiri Raboch,1 Josef Pavlat,1 Jana Uhrova,2 Hana Benakova,2 Tomas Zima2 1Center for Neuropsychiatric Research of Traumatic Stress, Department of Psychiatry and UHSL, 2Department of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic Abstract: Recent evidence indicates that the nature of interactions between the nervous system and immune system is important in the pathogenesis of depression. Specifically, alterations in pro-inflammatory cytokines have been related to the development of several psychological and neurobiological manifestations of depressive disorder, as well as to stress exposure. A number of findings point to tumor necrosis factor alpha (TNF-α as one of the central factors in these processes. Accordingly, in the present study, we test the hypothesis that specific influences of chronic stressors related to traumatic stress and dissociation are related to alterations in TNF-α levels. We performed psychometric measurement of depression (Beck Depression Inventory [BDI]-II, traumatic stress symptoms (Trauma Symptom Checklist [TSC]-40, and psychological and somatoform dissociation (Dissociative Experiences Scale [DES] and Somatoform Dissociation Questionnaire [SDQ]-20, respectively, and immunochemical measure of serum TNF-α in 66 inpatients with unipolar depression (mean age 43.1 ± 7.3 years. The results show that TNF-α is significantly related to DES (Spearman R=−0.42, P<0.01, SDQ-20 (Spearman R=−0.38, P<0.01, and TSC-40 (Spearman R=−0.41, P<0.01, but not to BDI-II. Results of the present study suggest that TNF-α levels are related to dissociative symptoms and stress exposure in depressed patients. Keywords: depression, dissociation, TNF-alpha, traumatic stress

  1. Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha.

    Science.gov (United States)

    Lotrich, Francis E; Ferrell, Robert E; Rabinovitz, Mordechai; Pollock, Bruce G

    2010-07-01

    Inflammatory cytokines may influence both labile anger and depression. Both psychiatric conditions can occur during interferon alfa-based treatments. Evidence also indicates a central nervous system role for tumor necrosis factor alpha (TNF-alpha), whose expression may be increased by interferon alfa. A polymorphism in the promoter region of TNF-alpha has been associated with various inflammatory illnesses. We therefore hypothesized that this TNF-alpha polymorphism would influence susceptibility to psychiatric symptoms during interferon alfa therapy. One hundred five patients with hepatitis C, initially without active major depression (major depressive disorder), were treated with interferon alfa and then prospectively monitored using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Beck Depression Inventory II, the Anger Irritability and Assault Questionnaire, and circulating TNF-alpha levels. The A-308G polymorphism (rs1800629) was determined using the 5'-nuclease assay. Repeated-measure mixed-effect analyses compared changes in symptoms over time. Beck Depression Inventory II score increased during interferon alfa therapy (F = 6.2; P depression incidence (chi = 0.0; P = 0.99) or increased Beck Depression Inventory II (F = 1.2; P = 0.31). Labile anger was not predicted by the serotonin transporter polymorphism (F = 0.8; P = 0.59). During treatment with an exogenous cytokine, vulnerability to worsening labile anger-distinct from major depression-is associated with genetic variability in TNF-alpha. This has implications both for patients being treated with interferon alfa and our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.

  2. High fat diet sensitizes fibromyalgia-like pain behaviors in mice via tumor necrosis factor alpha.

    Science.gov (United States)

    Tian, Dan; Tian, Miao; Zhang, Leilei; Zhao, Peng; Cui, Yunfeng; Li, Jinlong

    2018-01-01

    Fibromyalgia (FM) and obesity are closely related. However, little is known about how obesity contributes to FM. Importantly, adequate evidence has shown that tumor necrosis factor alpha (TNF-α) plays a critical role in obesity. Thus, we hypothesized that obesity-induced TNF-α release may potentiate FM-associated pain. To test this hypothesis, we investigated the role of TNF-α in the development of FM-like pain in a mouse model of acid saline injection-induced FM. Consistent with previous reports, we showed that repeated acid saline injections induced bilateral mechanical hyperalgesia, and this effect lasted for at least 4 days after acid saline injections. This phenomenon was associated with increased levels of TNF-α in plasma, muscles, and spinal cord. Furthermore, we found that 24 weeks of high fat diet treatment significantly potentiated acid saline-induced bilateral mechanical hyperalgesia. High fat diet-treated mice exhibited robustly increased levels of TNF-α in plasma, muscles, and spinal cord after acid saline injections compared with low fat diet-treated mice. Additionally, using immunofluorescence staining, we found that the number of TNF-α positive cells in dorsal root ganglion (DRG) was increased after acid saline injections, and high fat diet treatment further sensitized this increase. Finally, we reported that acid saline-induced FM-like pain behaviors were abolished in TNFRp55-/- mice, confirming the critical role of TNF-α in the development of FM-like pain. Taken together, our results suggested that high fat diet treatment may sensitize acid saline-induced FM-like pain via increasing TNF-α levels in plasma, muscles, and DRG.

  3. Estimation of salivary tumor necrosis factor-alpha in chronic and aggressive periodontitis patients.

    Science.gov (United States)

    Varghese, Sheeja S; Thomas, Hima; Jayakumar, N D; Sankari, M; Lakshmanan, Reema

    2015-09-01

    Periodontitis is a chronic bacterial infection characterized by persistent inflammation, connective tissue breakdown and alveolar bone destruction mediated by pro-inflammatory mediators. Tumor necrosis factor-alpha (TNF-α) is an important pro-inflammatory mediator that produced causes destruction of periodontal tissues. The aim of the study is to estimate the salivary TNF-α in chronic and aggressive periodontitis and control participants and further correlate the levels with clinical parameter such as gingival index (GI), plaque index (PI), probing pocket depth (PPD) and clinical attachment loss. The study population consisted of 75 subjects age ranging from 25 to 55 years attending the outpatient section of Department of Periodontics, Saveetha Dental College and Hospital. The study groups included Groups 1, 2, and 3 with participants with healthy periodontium (n = 25), generalized chronic periodontitis (n = 25) and generalized aggressive periodontitis (n = 25), respectively. Salivary samples from the participants were used to assess the TNF-α levels using enzyme-linked immunosorbent assay. GI and PI were found to be significantly higher in chronic and aggressive periodontitis compared to the controls. The mean TNF-α value in chronic periodontitis patients (12.92 ± 17.21 pg/ml) was significantly higher than in control subjects (2.15 ± 3.60 pg/ml). Whereas, in aggressive periodontitis patients the mean TNF-α (7.23 ± 7.67) were not significantly different from chronic periodontitis or healthy subjects. Among periodontitis participants, aggressive periodontitis subjects exhibited a significant positive correlation between the salivary TNF-α and PPD. Salivary TNF-α levels are significantly higher in chronic periodontitis than in healthy subjects, but there was no significant correlation with the clinical parameters.

  4. Circulating tumour necrosis factor alpha & soluble TNF receptors in patients with Guillain-Barre syndrome.

    Science.gov (United States)

    Radhakrishnan, V V; Sumi, M G; Reuben, S; Mathai, A; Nair, M D

    2003-05-01

    Tumour necrosis factor-alpha (TNF-alpha) is regarded as one of the immune factors that can induce demyelination of peripheral nerves in patients with Guillian-Barre syndrome (GBS). This present study was undertaken to find out the role of TNF-alpha and soluble TNF receptors in the pathogenesis of GBS; and to study the effect of intravenous immunoglobulin (ivIg) therapy on the serum TNF-alpha and soluble TNF receptors in patients with GBS. Thirty six patients with GBS in progressive stages of motor weakness were included in this study. The serum TNF-alpha and soluble TNF receptors (TNF-RI, TNF-RII) were measured in the serum samples of these patients before and after ivIg therapy by a sandwich ELISA. Of the 36 patients with GBS, 26 (72.2%) showed elevated serum TNF-alpha levels prior to ivIg therapy. Following a complete course of ivIg therapy there was a progressive decrease in the serum TNF-alpha concentrations in these 26 patients. On the other hand, the soluble TNF receptors, particularly TNF-RII showed an increase in the serum of GBS patients following ivIg therapy. The results indicate that ivIg reduces the serum TNF-alpha concentrations in the GBS patients having elevated levels prior to ivIg therapy. Elevated serum levels of soluble TNF receptors following ivIg therapy may play a protective role by inhibiting the demyelinating effect of TNF-alpha in the peripheral nerves of patients with GBS.

  5. Induction of endogenous tumor necrosis factor-alpha: suppression of centrally stimulated gastric motility.

    Science.gov (United States)

    Hermann, G E; Tovar, C A; Rogers, R C

    1999-01-01

    Gastric stasis is frequently seen in conjunction with critical infectious illness, chronic inflammatory disorders, radiation sickness, and carcinogenesis. These conditions are associated with elevated circulating levels of the cytokine tumor necrosis factor-alpha (TNF-alpha). The present studies examined the relationship between endogenously produced TNF-alpha and the central neural mechanisms that augment gastric motility. Systemic lipopolysaccharide (LPS) was employed to induce TNF-alpha production in thiobutabarbital-anesthetized rats. Sixty minutes after intravenous LPS injection, gastric motility could not be stimulated by a potent centrally acting gastrokinetic stimulant, thyrotropin-releasing hormone (TRH). This failure to elicit gastric motility via central mechanisms coincided with high circulating levels of TNF-alpha. However, intravenous injections of bethanecol, a peripherally acting cholinergic agonist with direct gastrokinetic effects, were still able to elicit normal increases in gastric motility in the presence of TNF-alpha and LPS. Therefore, the inability to stimulate gastric motility via central TRH could not be attributed to the direct inhibitory effects of either LPS or TNF-alpha on the stomach. If the production of endogenous TNF-alpha was suppressed via the use of urethan as the anesthetic agent, then intravenous injections of LPS were no longer effective in suppressing gastric motility. Thus these effects on gastric motility are not directly attributable to LPS nor are they due to direct effects on the gastric smooth muscle. Our previous study demonstrated that microinjection of femtomole quantities of TNF-alpha in the brain stem dorsal vagal complex (DVC) can modulate gastric motility. This central TNF-alpha effect on gastric motility was dose dependent and required an intact vagal efferent pathway. The results from these two studies suggest that systemically produced TNF-alpha may gain access to the DVC to modulate gastric function.

  6. Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination.

    Science.gov (United States)

    Zhan, Shuqin; Cai, Guo-Qiang; Zheng, Anni; Wang, Yuping; Jia, Jianping; Fang, Haotian; Yang, Youfeng; Hu, Meng; Ding, Qiang

    2011-04-01

    Recent studies recognize that Hypocretin system (also known as Orexin) plays a critical role in sleep/wake disorders and feeding behaviors. However, little is known about the regulation of the Hypocretin system. It is also known that tumor necrosis factor alpha (TNF-α) is involved in the regulation of sleep/wake cycle. Here, we test our hypothesis that the Hypocretin system is regulated by TNF-α. Prepro-Hypocretin and Hypocretin receptor 2 (HcrtR2) can be detected at a very low level in rat B35 neuroblastoma cells. In response to TNF-α, Prepro-Hypocretin mRNA and protein levels are down-regulated, and also HcrtR2 protein level is down-regulated in B35 cells. To investigate the mechanism, exogenous rat Prepro-Hypocretin and rat HcrtR2 were overexpressed in B35 cells. In response to TNF-α, protein and mRNA of Prepro-Hypocretin are significantly decreased (by 93% and 94%, respectively), and the half-life of Prepro-Hypocretin mRNA is decreased in a time- and dose-dependent manner. The level of HcrtR2 mRNA level is not affected by TNF-α treatment; however, HcrtR2 protein level is significantly decreased (by 86%) through ubiquitination in B35 cells treated with TNF-α. Downregulation of cellular inhibitor of apoptosis protein-1 and -2 (cIAP-1 and -2) abrogates the HcrtR2 ubiquitination induced by TNF-α. The control green fluorescent protein (GFP) expression is not affected by TNF-α treatment. These studies demonstrate that TNF-α can impair the function of the Hypocretin system by reducing the levels of both Prepro-Hypocretin and HcrtR2. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Evidence of a role of tumor necrosis factor alpha in refractory asthma.

    Science.gov (United States)

    Berry, Mike A; Hargadon, Beverley; Shelley, Maria; Parker, Debbie; Shaw, Dominick E; Green, Ruth H; Bradding, Peter; Brightling, Christopher E; Wardlaw, Andrew J; Pavord, Ian D

    2006-02-16

    The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma. We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study. As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01). Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.). Copyright 2006 Massachusetts Medical Society.

  8. Pharmacokinetics and tissue distribution of recombinant human tumor necrosis factor-alpha in mice

    International Nuclear Information System (INIS)

    Ferraiolo, B.L.; Moore, J.A.; Crase, D.; Gribling, P.; Wilking, H.; Baughman, R.A.

    1988-01-01

    The serum pharmacokinetics and the major organs of accumulation of recombinant human tumor necrosis factor-alpha (rHuTNF) were determined in BDF1 mice after intravenous and intramuscular administration. Serum concentrations of immunoreactive protein were determined by enzyme-linked immunosorbent assay, and radioactivity was quantitated by beta and gamma scintigraphy. The serum pharmacokinetics of labeled and unlabeled rHuTNF were identical when administered by the intravenous route. After intravenous doses of 165 to 320 micrograms/kg, the clearance was 2.9-3.6 ml/hr, the initial volume of distribution was 1.4-1.6 ml (70-80 ml/kg), and the half-life was 18.5-19.2 min. Intramuscular administration of 320 micrograms/kg resulted in a peak serum concentration of 112 ng/ml. The time of the peak concentration was 1 hr, and the bioavailability of the intramuscular dose was 12%. The data suggest that the disposition of this protein may be biexponential. If this is the case, the terminal phase would appear to account for less than 1% of the total AUC. Since serum concentrations in the terminal phase are at the sensitivity limit of the assay, a single half-life is reported. 125I-Labeled and metabolically labeled 3H-rHuTNF were used to examine tissue distribution. After intravenous 125I-rHuTNF administration, the rank order of accumulation of the 125I-radiolabel in the major organs (per cent dose per organ over 1440 min) was: liver greater than kidney greater than lung greater than heart greater than spleen. This rank order of accumulation was confirmed by intravenous 3H-rHuTNF administration

  9. Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.

    Science.gov (United States)

    Amaral, Maria E; Barbuio, Raquel; Milanski, Marciane; Romanatto, Talita; Barbosa, Helena C; Nadruz, Wilson; Bertolo, Manoel B; Boschero, Antonio C; Saad, Mario J A; Franchini, Kleber G; Velloso, Licio A

    2006-07-01

    Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.

  10. Tumour necrosis factor-alpha contributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia

    Czech Academy of Sciences Publication Activity Database

    Chytilová, Anna; Borchert, Gudrun H.; Mandíková-Alánová, Petra; Hlaváčková, Markéta; Kopkan, L.; Khan, M. A. H.; Imig, J. D.; Kolář, František; Neckář, Jan

    2015-01-01

    Roč. 241, č. 1 (2015), s. 97-108 ISSN 1748-1708 R&D Projects: GA ČR(CZ) GA13-10267S; GA ČR(CZ) GAP303/12/1162 Institutional support: RVO:67985823 Keywords : chronic hypoxia * ischaemia/reperfusion injury * reactive oxygen species * tumor necrosis factor - alpha Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.066, year: 2015

  11. The repeatability of interleukin-6, tumor necrosis factor-α, and C-reactive protein in COPD patients over one year

    Directory of Open Access Journals (Sweden)

    Umme Kolsum

    2009-04-01

    Full Text Available Umme Kolsum, Kay Roy, Cerys Starkey, Zoë Borrill, Nick Truman, Jørgen Vestbo, Dave SinghNorth West Lung Research Centre, University of Manchester, South Manchester University Hospitals Trust, Wythenshawe, Manchester, UKBackground: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and C-reactive protein (CRP over one year and examined the relationships between these systemic markers in COPD.Methods: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-α were measured. Repeatability was expressed by intraclass correlation coefficient (Ri and the Bland–Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits.Results: There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001 between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α. CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively. There were no other significant associations between the systemic markers at either of the visits.Conclusions: Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients. We have also shown that a robust and repeatable association between IL-6 and CRP exists.Keywords: interleukin-6, tumor necrosis factor-α, C-reactive protein, repeatability, COPD   

  12. The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

    Science.gov (United States)

    Luan, Y Y; Yao, Y M; Sheng, Z Y

    2013-01-01

    Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

  13. Elevated levels of plasma tumor necrosis factor alpha in patients with pseudoexfoliation glaucoma

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    Kondkar AA

    2018-01-01

    Full Text Available Altaf A Kondkar,1 Taif A Azad,1 Faisal A Almobarak,1 Hatem Kalantan,1 Saleh A Al-Obeidan,1 Khaled K Abu-Amero1,2 1Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA Background: Tumor necrosis factor alpha (TNF-α is a pro-inflammatory cytokine, which plays a role in glaucomatous neurodegeneration. Based on the plausible role of inflammation in the pathogenesis of pseudoexfoliation glaucoma (PEG, we investigated whether there is any relationship between the levels of plasma TNF-α and PEG or any of its clinical indices in comparison to normal controls.Methods: The study was designed as a retrospective analysis. Plasma samples from 49 PEG patients and 88 non-glaucomatous controls were evaluated for TNF-α levels using an enzyme-linked immunosorbent assay (ELISA. The assay was performed in duplicates on a biochemical/ELISA analyzer.Results: The two study groups were similar in age, sex and systemic disease distribution. The mean TNF-α concentration was significantly higher in the PEG patients (5.54±4.58 pg/mL than in the control subjects (0.93±1.49 pg/mL; 95% confidence interval [CI] =3.50–5.72; p=0.000. The overall dose–response trend was significant (χ2=57.07, df=2; p=0.000. A moderate positive and significant correlation was seen between TNF-α level and cup/disc ratio, an important clinical index for PEG. Besides, binary logistic regression analysis showed that the risk of PEG was most significantly affected by TNF-α level as compared to no association with age and sex. In receiver operating characteristic analysis, the area under the curve was 0.777 (95% CI =0.682–0.872 and statistically significant (p=0.000.Conclusion: Elevated systemic levels of inflammatory marker, TNF-α, are associated with PEG and may possibly serve as a biomarker for undiagnosed early

  14. Tumor necrosis factor alpha rs1800629 polymorphism and risk of cervical lesions: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available BACKGROUND: Tumor necrosis factor- alpha (TNF-α is an inflammatory cytokine which may play important role on the immune response may control the progression of cervical lesions. There is a possible association between TNF-α rs1800629 G/A polymorphism and cervical lesions, but previous studies report conflicting results. We performed a meta-analysis to comprehensively assess the association between TNF-α rs1800629 polymorphism and cervical lesions risk. METHODS: Literature searches of Pubmed, Embase, Web of Science, and Wanfang databases were performed for all publications on the association between TNF-α rs1800629 polymorphism and cervical lesions through December 15, 2012. The pooled odds ratios (ORs with their 95% confidence interval (95%CIs were calculated to assess the strength of the association. RESULTS: Twenty individual case-control studies from 19 publications with a total of 4,146 cases and 4,731 controls were finally included into the meta-analysis. Overall, TNF-α rs1800629 polymorphism was significantly associated with increased risk of cervical lesions under two main genetic comparison models (For A versus G: OR 1.22, 95%CI 1.04-1.44, P = 0.017; for AA versus GG: OR 1.32, 95%CI 1.02-1.71, P = 0.034. Subgroup analysis by ethnicity further showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical lesions in Caucasians but not in Asians. Subgroup analysis by the types of cervical lesions showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical cancer (For A versus G: OR 1.24, 95%CI 1.05-1.47, P = 0.011; for AA versus GG: OR 1.31, 95%CI 1.01-1.70, P = 0.043; for AA/GA versus GG: OR 1.25, 95%CI 1.01-1.54, P = 0.039. CONCLUSION: The meta-analysis suggests that TNF-α rs1800629 polymorphism is associated with increased risk of cervical lesions, especially in Caucasians.

  15. Quality and completeness of utilisation data on biological agents across European countries: tumour necrosis factor alpha inhibitors as a case study.

    NARCIS (Netherlands)

    Hoebert, J.M.; Mantel-Teeuwisse, A.K.; Dijk, L. van; Laing, R.O.; Leufkens, H.G.M.

    2011-01-01

    PURPOSE: For optimal decision making on access to and regulations around biologicals availability of national utilisation data is a prerequisite. This study characterises the main categories of critical issues in collecting available national utilisation data on tumour necrosis factor alpha

  16. Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea.

    Science.gov (United States)

    Shin, Suk Pyo; Kim, Nam Keun; Kim, Ju Hwan; Lee, Ju Ho; Kim, Jung Oh; Cho, Sung Hwan; Park, Hana; Kim, Mi Na; Rim, Kyu Sung; Hwang, Seong Gyu

    2015-12-14

    To investigate associations between the tumor necrosis factor alpha (TNF-α) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea. Hepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms, which are TNF-α -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-α genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC. None of the TNF-α polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-α -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-α -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-α -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-α -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-α -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-α -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-α -1031/-238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-α -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323). Although no single TNF-α polymorphism is associated with HCC in this study, some TNF-α genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases

  17. 2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats.

    Science.gov (United States)

    Igarashi, T; Kikuchi, S; Shubayev, V; Myers, R R

    2000-12-01

    This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo. Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli. Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia. The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots. The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.

  18. Impact of tobacco smoking on response to tumour necrosis factor-alpha inhibitor treatment in patients with ankylosing spondylitis

    DEFF Research Database (Denmark)

    Glintborg, Bente; Højgaard, Pil; Lund Hetland, Merete

    2016-01-01

    OBJECTIVES: To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses in patients with AS treated with their first tumour necrosis factor-alpha inhibitor (TNFi) therapy in routine care. METHODS: Observational cohort study based...... AS patients included in the study, 1425(90%) had known smoking status (current/never/previous: 43%/41%/16%). The median follow-up time was 2.02 years (IQR 0.69-5.01). At baseline, current smokers compared with never smokers had longer disease duration (4 years (1-12)/2 years (0-10)), higher BASDAI (61 mm (47...

  19. Increased interleukin 6 and tumour necrosis factor α expression in the infrapatellar fat pad of the knee joint with the anterior knee pain syndrome: a preliminary report.

    Science.gov (United States)

    Witoński, Dariusz; Wągrowska-Danilewicz, Małgorzata; Kęska, Rafał; Raczyńska-Witońska, Grażyna; Stasikowska-Kanicka, Olga

    2010-01-01

    The pathway of pain in the anterior knee pain syndrome remains unclear. It has been hypothesized that some biochemical mediators of inflammation, such as cytokines contribute to the process. The objective of this work was to evaluate the synovial membrane and the infrapatellar fat pad expression of the inflammatory mediators and potentially chondrodestructive cytokines interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α) in the anterior knee pain syndrome, and to determine whether the cytokine expression counterpart with/corresponds to the amount of chondral damage in this syndrome. Ten consecutive patients with the anterior knee pain syndrome (group I) participated in the study. Patients with a history of trauma were excluded from this group. For comparison we used 10 patients with anterior cruciate ligament rupture or meniscal lesion with no history of pain in the anterior compartment (group II). Immunohistochemical techniques using a polyclonal rabbit anti-human antibody to IL-6 and a monoclonal mouse anti-human antibody to TNF-α were employed. The results show a statistically significant higher expression of IL-6 in infrapatellar fat pad (p anterior knee pain syndrome could be characterized by infrapatellar fat pad and synovial inflammation variations without the articular cartilage loss.

  20. Tumor Necrosis Factor-α and Interleukin-6: Potential Interorgan Inflammatory Mediators Contributing to Destructive Periodontal Disease in Obesity or Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Roozbeh Khosravi

    2013-01-01

    Full Text Available Obesity has become a worldwide health burden in the last two decades. Obesity has been associated with increased comorbidities, such as coronary artery disease, diabetes, and destructive periodontal disease. Obesity is also part of a group of risk factors occurring together in an individual, which is referred to as metabolic syndrome. Clinical studies have shown higher risk for destructive periodontal disease in obesity and metabolic syndrome. However, the role of obesity and metabolic syndrome in the onset and development of destructive periodontal disease has not yet been fully understood. In this review, we discuss a working model, which focuses on interorgan inflammation as a common etiological factor for destructive periodontal disease associated with obesity and metabolic syndrome. Specifically, we suggest that elevated levels of tumor necrosis factor-α (TNF-α or interleukin 6 (IL-6—both adipokines and known risk factors for destructive periodontal disease—in obesity and metabolic syndrome contribute to the onset and development of destructive periodontal disease. The connections between destructive periodontal disease and systemic conditions, such as obesity or metabolic syndrome, are complex and potentially multidirectional. This review largely focuses on TNF-α and IL-6, inflammatory mediators, as potential common risk factors and does not exclude other biological mechanisms.

  1. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis.

    Science.gov (United States)

    Albrecht, Lea-Jessica; Tauber, Simone C; Merres, Julika; Kress, Eugenia; Stope, Matthias B; Jansen, Sandra; Pufe, Thomas; Brandenburg, Lars-Ove

    2016-01-01

    The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6(-/-), TNFR1(-/-), and TNFR1-IL-6(-/-) KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1(-/-), IL-6(-/-), and TNFR1-IL-6(-/-) mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1(-/-) and TNFR1-IL-6(-/-) mice in contrast to IL-6(-/-) and wild type mice. Furthermore, the increased mortality of TNFR1(-/-) and TNFR1-IL-6(-/-) mice correlated with decreased glial cell activation compared to IL-6(-/-) or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

  2. Clinical significance of changes of plasma concentration of endothelium and serum levels of interleukin-6 and tumor necrosis factor in patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Xie Jianping; Zhang Guoyuan; Li Suping; Wu Chenxiu; Sun Yuejun; Yan Zongxun

    2003-01-01

    Objective: To determine the changes of plasma endothelium (ET) and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) concentrations in patients with type 2 diabetes mellitus. Methods: Plasma ET and serum IL-6 and TNF-α levels were measured by radioimmunoassay in 61 cases of type 2 diabetes mellitus (DM) 36 without complication and 25 cases with complications and 33 controls. Results: (1) The plasma levels of ET and serum levels of IL-6 and TNF-α in patients with type 2 diabetes mellitus were significantly higher than those in the controls (p<0.01); (2) The blood levels of ET, TNF-α in patients with complications were significantly higher than those in patients without complications (p<0.02); (3) The blood levels of ET, IL-6 and TNF-α were mutually positively correlated. Conclusion: Monitoring of ET, IL-6 and TNF-α levels in diabetic patients can provide additional valuable information for assessing the course of disease and efficacy of management

  3. Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

    Directory of Open Access Journals (Sweden)

    Claudia Hernández-Jiménez

    Full Text Available The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5, mechanical ventilation with dry oxygen dispensation, and Group II (n = 5, mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77. This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05. Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02. Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

  4. Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

    Science.gov (United States)

    Hernández-Jiménez, Claudia; García-Torrentera, Rogelio; Olmos-Zúñiga, J Raúl; Jasso-Victoria, Rogelio; Gaxiola-Gaxiola, Miguel O; Baltazares-Lipp, Matilde; Gutiérrez-González, Luis H

    2014-01-01

    The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

  5. LPS-stimulated tumor necrosis factor-alpha and interleukin-6 mRNA and cytokine responses following acute psychological stress.

    Science.gov (United States)

    Huang, Chun-Jung; Stewart, Jennifer K; Franco, R Lee; Evans, Ronald K; Lee, Zendra P; Cruz, Tracey Dawson; Webb, Heather E; Acevedo, Edmund O

    2011-11-01

    The purpose of this study was to examine the effect of acute psychological stress on LPS-stimulated TNF-α and IL-6 mRNA expression. Twenty-one healthy male subjects participated in 20 min of acute stress. Blood samples for norepinephrine and LPS-stimulated TNF-α and IL-6 cytokines and mRNA were drawn prior to, immediately after and 1-h after stress. Stress-induced increases in anxiety scores, cortisol, plasma norepinephrine, and heart rate demonstrated that the experimental protocol elicited an acute stress response. LPS-stimulated TNF-α mRNA decreased significantly immediately post-stress and partially recovered at 1h post-stress, whereas LPS-stimulated IL-6 mRNA exhibited a significant change across time, with an increase immediately after stress and a decrease 1h after stress. Trends in LPS-stimulated TNF-α and IL-6 cytokine concentrations followed the patterns of mRNA expression. A negative correlation of body mass index (BMI) and percent change of LPS-stimulated TNF-α mRNA was observed immediately post-stress, and BMI positively correlated with percent change of LPS-stimulated IL-6 cytokine levels immediately following stress. These findings demonstrated that acute psychological stress affects LPS-stimulated IL-6 and TNF-α gene expression. These results also indicate that BMI may impact the effects of psychological stress on cytokine responses to immune challenge. Further examination of the effects of stress on synthesis of other cellular cytokines and investigation of the association of BMI and stress responses will provide a more clear representation of the cytokine responses to acute psychological stress. In addition, studies examining the influence of gender on the response of immune cell subsets to acute stress and the possible mediating effect of BMI are warranted. Published by Elsevier Ltd.

  6. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women : the Health ABC Study

    NARCIS (Netherlands)

    Visser, Marjolein; Pahor, Marco; Taaffe, Dennis R; Goodpaster, Bret H; Simonsick, Eleanor M; Newman, Anne B; Nevitt, Michael; Harris, Tamara B

    BACKGROUND: A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show a relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers of inflammation are associated with muscle mass and

  7. Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor α: a meta-analysis.

    Science.gov (United States)

    Li, Kelei; Huang, Tao; Zheng, Jusheng; Wu, Kejian; Li, Duo

    2014-01-01

    Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m². The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended.

  8. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2016-01-01

    Full Text Available The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6−/−, TNFR1−/−, and TNFR1-IL-6−/− KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1−/−, IL-6−/−, and TNFR1-IL-6−/− mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1−/− and TNFR1-IL-6−/− mice in contrast to IL-6−/− and wild type mice. Furthermore, the increased mortality of TNFR1−/− and TNFR1-IL-6−/− mice correlated with decreased glial cell activation compared to IL-6−/− or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

  9. IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes

    DEFF Research Database (Denmark)

    Falkencrone, Sidsel; Poulsen, Lars K.; Bindslev-Jensen, Carsten

    2013-01-01

    IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have...

  10. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Nirmala Chandralega Kampan

    2017-11-01

    Full Text Available BackgroundEpithelial ovarian cancer (EOC remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2, as well as pro-inflammatory factors such as interleukin 6 (IL-6 and tumor necrosis factor (TNF. IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs.MethodsAscites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control. In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2+ Tregs and TNFR2− Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.ResultsHigh levels of immunosuppressive (sTNFR2, IL-10, and TGF-β and pro-inflammatory cytokines (IL-6 and TNF were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4+CD25hiFoxP3+ Tregs, resulting in an increased TNFR2+ Treg/effector T cell ratio. Furthermore, TNFR2+ Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2+ Treg frequency was inversely correlated with interferon-gamma (IFN-γ production by effector T cells, and was

  11. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells.

    Science.gov (United States)

    Kampan, Nirmala Chandralega; Madondo, Mutsa Tatenda; McNally, Orla M; Stephens, Andrew N; Quinn, Michael A; Plebanski, Magdalena

    2017-01-01

    Epithelial ovarian cancer (EOC) remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs) in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2), as well as pro-inflammatory factors such as interleukin 6 (IL-6) and tumor necrosis factor (TNF). IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs. Ascites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control). In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2 + Tregs and TNFR2 - Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC. High levels of immunosuppressive (sTNFR2, IL-10, and TGF-β) and pro-inflammatory cytokines (IL-6 and TNF) were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4 + CD25 hi FoxP3 + Tregs, resulting in an increased TNFR2 + Treg/effector T cell ratio. Furthermore, TNFR2 + Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2 + Treg frequency was inversely correlated with interferon-gamma (IFN-γ) production by effector T cells, and was uniquely able to suppress TNFR2

  12. Tumour necrosis factor-alpha (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Jónasdóttir, O; Petersen, J; Bendtzen, K

    2001-01-01

    Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor alpha (TNFalpha) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFa are mediated by TNF receptors (TNF......-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNFalpha actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNFalpha, TNFbeta, now termed lymphotoxin (LTalpha), and sTNF-R1 and sTNF-R2 were measured by ELISA in 8 patients with WG during...... active disease and during immunosuppressive treatment, and in 11 healthy controls in parallel. Serum concentrations of TNFalpha were undetectable in all except two controls (18%) and three patients with WG (37%). After 7 days of therapy, six of the WG patients had measurable TNFalpha levels. Examination...

  13. Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Ainsworth, Mark; Steenholdt, Casper

    2009-01-01

    Antibody constructs targeting tumour necrosis factor-alpha (TNF) have become important in the management of several chronic immunoinflammatory diseases. Four recombinant anti-TNF drugs are currently approved for clinical use in patients with various chronic inflammatory diseases, three of which...... are effective in chronic inflammatory bowel disease. These proteins can dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favourably to anti-TNF antibodies. For example, patients suffering from Crohn's disease do not benefit from...... for circulating levels of functional anti-TNF drugs and ADAs is therefore warranted so that treatment can be tailored to the individual patient (individual medicine or personal medicine) in order that effective and economical long-term therapy can be given with minimal risks to the patients....

  14. Increased plasma levels of tumor necrosis factor-alpha in asymptomatic/"indeterminate" and Chagas disease cardiomyopathy patients

    Directory of Open Access Journals (Sweden)

    Renata Cristina Ferreira

    2003-04-01

    Full Text Available We compared plasma tumor necrosis factor-alpha (TNF-alpha levels among asymptomatic/"indeterminate" Chagas disease patients (ASY and patients across the clinical spectrum of chronic Chagas disease cardiomyopathy (CCC. Idiopathic dilated cardiomyopathy (DCM patients and normal controls (NC were included as controls. ASY Chagas disease patients had significantly higher plasma TNF-alpha levels than NC. TNF-alpha levels among severe CCC patients with significant left ventricular (LV dysfunction were similar to those of DCM patients, showing average 2-fold higher levels than CCC patients without LV dysfunction and ASY patients, and 8-fold higher levels than NC. In Chagas disease, chronic TNF-a production prior to heart failure may play a role in CCC progression.

  15. Characterization of a canine tetranucleotide microsatellite marker located in the first intron of the tumor necrosis factor alpha gene.

    Science.gov (United States)

    Watanabe, Masashi; Tanaka, Kazuaki; Takizawa, Tatsuya; Segawa, Kazuhito; Neo, Sakurako; Tsuchiya, Ryo; Murata, Michiko; Murakami, Masaru; Hisasue, Masaharu

    2014-01-01

    A polymorphic tetranucleotide (GAAT)n microsatellite in the first intron of the canine tumor necrosis factor alpha (TNFA) gene was characterized in this study; 139 dogs were analyzed: 22 Beagles, 26 Chihuahuas, 20 Miniature Dachshunds, 24 Miniature Poodles, 22 Pembroke Welsh Corgis and 25 Shiba Inus. We detected the presence of the 4 alleles (GAAT)5, (GAAT)6, (GAAT)7 and (GAAT)8, including 9 of the 10 expected genotypes. The expected heterozygosity (He) and the polymorphic information content (PIC) value of this microsatellite locus varied from 0.389 to 0.749 and from 0.333 to 0.682, respectively, among the 6 breeds. The allelic frequency differed greatly among breeds, but this microsatellite marker was highly polymorphic and could be a useful marker for the canine TNFA gene.

  16. Tumour necrosis factor-alpha (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Jónasdóttir, O; Petersen, J; Bendtzen, K

    2001-01-01

    Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor alpha (TNFalpha) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFa are mediated by TNF receptors (TNF......-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNFalpha actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNFalpha, TNFbeta, now termed lymphotoxin (LTalpha), and sTNF-R1 and sTNF-R2 were measured by ELISA in 8 patients with WG during...... of the relative amounts of TNFalpha and sTNF-R indicated that TNFalpha was mostly bound to its soluble receptors. In WG, the serum levels of sTNF-R1 and sTNF-R2 were dramatically increased (p...

  17. Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha.

    Science.gov (United States)

    Brock, C; Brock, B; Aziz, Q; Møller, H J; Pfeiffer Jensen, M; Drewes, A M; Farmer, A D

    2017-05-01

    The vagus nerve is a central component of cholinergic anti-inflammatory pathways. We sought to evaluate the effect of bilateral transcutaneous cervical vagal nerve stimulation (t-VNS) on validated parameters of autonomic tone and cytokines in 20 healthy subjects. 24 hours after t-VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor-α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t-VNS exerts an autonomic and a subtle antitumor necrosis factor-α effect, which warrants further evaluation in larger controlled studies. © 2016 John Wiley & Sons Ltd.

  18. Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha blocker

    Directory of Open Access Journals (Sweden)

    Agarwal Pankaj

    2007-01-01

    Full Text Available The development of anti-tumor necrosis factor (TNF therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

  19. Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey

    OpenAIRE

    De Bandt, Michel; Sibilia, Jean; Le Lo?t, Xavier; Prouzeau, Sebastian; Fautrel, Bruno; Marcelli, Christian; Boucquillard, Eric; Siame, Jean Louis; Mariette, Xavier; ,

    2005-01-01

    The development of drug-induced lupus remains a matter of concern in patients treated with anti-tumour necrosis factor (TNF) alpha. The incidence of such adverse effects is unknown. We undertook a retrospective national study to analyse such patients. Between June and October 2003, 866 rheumatology and internal medicine practitioners from all French hospital centres prescribing anti-TNF in rheumatic diseases registered on the website of the 'Club Rhumatismes et Inflammation' were contacted by...

  20. Suppression of interleukin-1[beta] and tumour necrosis factor-[alpha] biosynthesis by cadmium in in vitro activated human peripheral blood mononuclear cells

    Energy Technology Data Exchange (ETDEWEB)

    Theocharis, S.E. (Dept. of Experimental Pharmacology, School of Medicine, Univ. of Athens (Greece) First Dept. of Internal Medicine, School of Medicine, Univ. of Athens, Laikon Hospital (Greece)); Panayiotidis, P.G. (First Dept. of Internal Medicine, School of Medicine, Univ. of Athens, Laikon Hospital (Greece)); Souliotis, V.L. (National Hellenic Research Foundation, Inst. of Biological Research and Biotechnology, Athens (Greece))

    1994-12-01

    Cadmium is a highly toxic element responsible for acute and chronic toxicity in man. There is evidence that cadmium induces pathophysiological effects by modulating components of the immune system. Cytokines are being increasingly recognized as essential mediators of normal and pathologic immune responses. Cadmium at concentrations varying from 1.0x10[sup -4] to 3.3x10[sup -6] M inhibited the phytohemagglutinin induced production of interleukin-1[beta] and tumour necrosis factor-[alpha], in in vitro activated human peripheral blood mononuclear cells. The messenger RNA levels of interleukin-1[beta] and tumour necrosis factor-[alpha] were examined during a 24-h culture period, at different time points. The decreased messenger RNA levels at the time points of the maximum expression of interleukin-1[beta] and tumour necrosis factor-[alpha] indicate that cadmium suppresses their production at the transcriptional level. (orig.)

  1. Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on C-Reactive Protein, Interleukin 6 and Tumor Necrosis Factor α: A Meta-Analysis

    Science.gov (United States)

    Li, Kelei; Huang, Tao; Zheng, Jusheng; Wu, Kejian; Li, Duo

    2014-01-01

    Background Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). Methods and Findings A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m2. The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Conclusions Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended. PMID:24505395

  2. Alopecia secondary to anti-tumor necrosis factor-alpha therapy*

    Science.gov (United States)

    Ribeiro, Lara Beatriz Prata; Rego, Juliana Carlos Gonçalves; Estrada, Bruna Duque; Bastos, Paula Raso; Piñeiro Maceira, Juan Manuel; Sodré, Celso Tavares

    2015-01-01

    Biologic drugs represent a substantial progress in the treatment of chronic inflammatory immunologic diseases. However, its crescent use has revealed seldom reported or unknown adverse reactions, mainly associated with anti-tumor necrosis factor (anti-TNF). Psoriasiform cutaneous reactions and few cases of alopecia can occur in some patients while taking these drugs. Two cases of alopecia were reported after anti-TNF therapy. Both also developed psoriasiform lesions on the body. This is the second report about a new entity described as 'anti-TNF therapy-related alopecia', which combines clinical and histopathological features of both alopecia areata and psoriatic alopecia. The recognition of these effects by specialists is essential for the proper management and guidance of these patients. PMID:25830994

  3. Tumor necrosis factor-alpha antagonism improves vasodilation during hyperinsulinemia in metabolic syndrome.

    Science.gov (United States)

    Tesauro, Manfredi; Schinzari, Francesca; Rovella, Valentina; Melina, Domenico; Mores, Nadia; Barini, Angela; Mettimano, Marco; Lauro, Davide; Iantorno, Micaela; Quon, Michael J; Cardillo, Carmine

    2008-07-01

    Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha. We assessed the effects of TNF-alpha neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome. Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab. Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab. TNF-alpha neutralization ameliorates vascular reactivity in metabolic syndrome during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients.

  4. Tumor necrosis factor-alpha inhibition and VATER association: a causal relationship.

    Science.gov (United States)

    Carter, John D; Valeriano, Joanne; Vasey, Frank B

    2006-05-01

    Inflammatory conditions that may require the use of a tumor necrosis factor-a (TNF-a) antagonist often involve women of child-bearing age. TNF-a antagonists are presumed to be safe in pregnancy based on animal data. However, this has never been formally studied in prospective trials involving humans. We describe a patient with psoriasis and psoriatic arthritis who took etanercept 50 mg subcutaneously (SQ) twice weekly throughout her pregnancy. She gave birth to a child with VATER association. Animal and human data exist to suggest a possible causal relationship between the mother's use of etanercept and the child's development of VATER association. We propose that the TNF antagonists, specifically etanercept, be used with caution in pregnant women. Patient registries of women who take TNF-a antagonists during pregnancy also need to be followed to see if there is an increase in the birth defects that are part of VATER association.

  5. Immunomagnetic separation of tumor necrosis factor alpha. II. In situ procedure for the human gingival space.

    Science.gov (United States)

    Rossomando, E F; White, L B; Hadjimichael, J

    1992-11-27

    An in situ procedure has been developed for the separation of tumor necrosis factor (TNF) alpha directly from the fluid in the human gingival space. Paramagnetic beads coated with anti-TNF monoclonal antibodies were introduced into the gingival space of the subject with a polypropylene-tipped calibrated delivery system and retrieved using a permanent magnet designed to fit into the space. After retrieval, the amount of immunoadsorbed TNF was quantified using an immunochemical assay called the "cluster assay". The results indicate that following the appropriate preparation of the site, over 95% of the beads could be recovered. With this method we found that 62% of those cavities sampled contained TNF and that the values ranged from 0.10 to 13.0 ng/ml with a mean value of 1.7 ng/ml. A comparison of these values with those obtained from the same space using other methods suggests that the immunomagnetic method was more effective in retrieval of TNF. Because the separation is performed in situ we have named the procedure "chromatobiosis".

  6. Activated astrocytes induce nitric oxide synthase-2 in cerebral endothelium via tumor necrosis factor alpha.

    Science.gov (United States)

    Shafer, R A; Murphy, S

    1997-12-01

    Astrocytes under pathological conditions become activated and produce a variety of cytokines and low molecular weight signal molecules. Previously we demonstrated that activated astrocytes release nitric oxide which can downregulate the expression of nitric oxide synthase (NOS)-2 in co-cultured cerebral endothelium, and also release a transcriptionally regulated factor that can induce NOS-2 expression in endothelium (Borgerding and Murphy: J Neurochem 65:1342, 1995). The activity of this NOS-2-inducing factor was impeded by inhibitors of tyrosine kinases and NF-kappaB activation. Tumor necrosis factor (TNF alpha) alone, or in combination with IL-6, induced NOS-2 expression in endothelial cells. A neutralizing antibody against TNF alpha attenuated the NOS-2 expression in endothelial cells exposed to activated astrocytes. These results imply that cytokine-activated astrocytes release TNF alpha which can induce NOS-2 expression in endothelium and suggest that activated astrocytes within the CNS may induce expression of NOS-2 in cells of the adjacent microvasculature. The ensuing alterations in blood-brain barrier properties may be either beneficial or detrimental.

  7. PROGNOSTIC VALUE OF TUMOR NECROSIS FACTOR-ALPHA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    E. N. Zotina

    2016-01-01

    Full Text Available The prognostic value of tumor necrosis factor-alfa (TNFα, a pro-inflammatory cytokine was studied in 140 patients with a newly diagnosed chronic lymphocytic leukemia (CLL. TNFα contents in blood serum was determined using ELISA method. A significant increase of serum TNFα was shown in patients with newly diagnosed CLL, as compared to healthy individuals. Dependence of the cytokine concentration on clnical stage and course of disease was revealed: the highest levels of serum TNFα were registered in patients with advanced disease and/or CLL progression. Distinct correlations were revealed between the studied cytokine amounts and clinical laboratory parameters reflecting the cell proliferative activity and tumor clone size. Immunochemotherapy was accompanied by a significant reduction of TNFα levels. According to the data from multivariate regression analysis. TNFα level of at the time of the diagnosis was an independent predictor of overall survival. Hence, TNFα plays an important role in CLL pathogenesis and may be used as an additional predictive factor for CLL outcomes.

  8. Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism

    Directory of Open Access Journals (Sweden)

    Jackson Lauren R

    2012-03-01

    Full Text Available Abstract Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P

  9. Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Madonna, Rosalinda [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Shelat, Harnath; Xue, Qun; Willerson, James T. [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States); De Caterina, Raffaele [Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Geng, Yong-Jian, E-mail: yong-jian.geng@uth.tmc.edu [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States)

    2009-10-15

    Cardiac stem cells are vulnerable to inflammation caused by infarction or ischemic injury. The growth factor, erythropoietin (Epo), ameliorates the inflammatory response of the myocardium to ischemic injury. This study was designed to assess the role of Epo in regulation of expression and activation of the cell death-associated intracellular signaling components in cardiac myoblasts stimulated with the proinflammatory cytokine tumor necrosis factor (TNF)-{alpha}. Cardiac myoblasts isolated from canine embryonic hearts characterized by expression of myocardin A, a promyogenic transcription factor for cardiovascular muscle development were pretreated with Epo and then exposed to TNF-{alpha}. Compared to untreated cells, the Epo-treated cardiac myoblasts exhibited better morphology and viability. Immunoblotting revealed lower levels of active caspase-3 and reductions in iNOS expression and NO production in Epo-treated cells. Furthermore, Epo pretreatment reduced nuclear translocation of NF-{kappa}B and inhibited phosphorylation of inhibitor of kappa B (I{kappa}B) in TNF-{alpha}-stimulated cardiac myoblasts. Thus, Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-{alpha} by inhibiting NF-{kappa}B-mediated iNOS expression and NO production and by preventing caspase-3 activation.

  10. Tumor necrosis factor-alpha and its receptors in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Jacek Nikliński

    2010-05-01

    Full Text Available The aim of the present study was to characterize the expression pattern of tumor necrosis factor (TNF-alpha and its receptors (TNF-Rs in the epithelial ovarian cancer (EOC and compare these results with the outcome of 126 patients. Presence of TNF-alpha, TNFR-1 and TNFR-2 were studied by Western blotting and immunohistochemistry. The proportion of samples positive for TNF-alpha and TNF-R2 was higher in epithelial ovarian cancer patients than in benign ovarian diseases (p<0.001 and p=0.016, respectively. Immunostaining intensity of TNF-R2 were correlated with tumor stage (p<0.001 and with reduced mean survival time (MST (p=0.002. The results of the present study suggested that tissue expression of TNF-R2 in epithelial ovarian cancer was correlated with the highest risk of cancer progression. Thus, the clinical value of activated TNF system in epithelial ovarian cancer needs to be further investigated.

  11. Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression.

    Science.gov (United States)

    MacParland, Sonya A; Ma, Xue-Zhong; Chen, Limin; Khattar, Ramzi; Cherepanov, Vera; Selzner, Markus; Feld, Jordan J; Selzner, Nazia; McGilvray, Ian D

    2016-06-15

    Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate

  12. Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma : Three time periods at risk for amputation

    NARCIS (Netherlands)

    van Ginkel, Robert J.; Thijssens, Katja M. J.; Pras, Elisabeth; van der Graaf, Winette T. A.; Suurmeijer, Albert J. H.; Hoekstra, Harald J.

    Background: The aim of this study was to investigate the long-term limb salvage rate and overall survival after isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma (STS). Methods: From 1991 to 2003, 73 patients (36 men, 37 women,

  13. Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma: three time periods at risk for amputation.

    NARCIS (Netherlands)

    Ginkel, R.J. van; Thijssens, K.M.; Pras, E.; Graaf, W.T.A. van der; Suurmeijer, A.J.H.; Hoekstra, H.J.

    2007-01-01

    BACKGROUND: The aim of this study was to investigate the long-term limb salvage rate and overall survival after isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma (STS). METHODS: From 1991 to 2003, 73 patients (36 men, 37 women,

  14. Value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin during hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan

    NARCIS (Netherlands)

    van Ginkel, RJ; Limburg, PC; Piers, DA; Hoekstra, HJ; Schraffordt Koops, H.

    Background: The aim of this study was to analyze the value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin (RISA) in patients treated with hyperthermic isolated limb perfusion with tumor necrosis factor-alpha (TNFalpha) and melphalan. Methods: Forty-eight

  15. Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

    NARCIS (Netherlands)

    Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

    Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

  16. Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Pedersen, SB

    2006-01-01

    Tumor necrosis factor alpha (TNF-alpha) stimulates lipolysis in man. We examined whether plasma TNF-alpha is associated with the degree by which insulin suppresses markers of lipolysis, for example, plasma free fatty acid (FFA) and net lipid oxidation (LIPOX) rate in HIV-infected patients...

  17. Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bernardino, Liliana; Xapelli, Sara; Silva, Ana P

    2005-01-01

    The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects of th...

  18. Reactivation of pulmonary tuberculosis (TBC) with the use of antagonist of the tumor necrosis factor alpha (FNTα) in rheumatoid arthritis: On purpose of a case

    International Nuclear Information System (INIS)

    Martinez V, Jose B; Medina V, Yimy F; Parga, Roberto; Restrepo, Jose Felix; Iglesias G, Antonio; Rondon, Federico

    2005-01-01

    Woman 56 years old, with history of rheumatoid arthritis who develops reactivation of pulmonary tuberculosis (TBC) after 1 year of treatment with biological therapy (antagonist of the tumor necrosis factor alpha). It is discussed pathophysiologic mechanisms, diagnostic approach, treatment of TBC and some recommendations for the use of biological therapy in patients with rheumatic disease

  19. The effect of a metalloproteinase inhibitor (GI5402) on tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha receptors during human endotoxemia

    NARCIS (Netherlands)

    Dekkers, P. E.; Lauw, F. N.; ten Hove, T.; te Velde, A. A.; Lumley, P.; Becherer, D.; van Deventer, S. J.; van der Poll, T.

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is released from the cell surface by cleavage of pro-TNF-alpha by metalloproteinases (MPs). In cell cultures, inhibition of MPs has been found not only to reduce the release of TNF-alpha, but also to enhance the surface expression of TNF-alpha and TNF-alpha

  20. Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey.

    Science.gov (United States)

    De Bandt, Michel; Sibilia, Jean; Le Loët, Xavier; Prouzeau, Sebastian; Fautrel, Bruno; Marcelli, Christian; Boucquillard, Eric; Siame, Jean Louis; Mariette, Xavier

    2005-01-01

    The development of drug-induced lupus remains a matter of concern in patients treated with anti-tumour necrosis factor (TNF) alpha. The incidence of such adverse effects is unknown. We undertook a retrospective national study to analyse such patients. Between June and October 2003, 866 rheumatology and internal medicine practitioners from all French hospital centres prescribing anti-TNF in rheumatic diseases registered on the website of the 'Club Rhumatismes et Inflammation' were contacted by email to obtain the files of patients with TNF-induced systemic lupus erythematosus. Twenty-two cases were collected, revealing two aspects of these manifestations. Ten patients (six patients receiving infliximab, four patients receiving etanercept) only had anti-DNA antibodies and skin manifestations one could classify as 'limited skin lupus' or 'toxidermia' in a context of autoimmunity, whereas 12 patients (nine patients receiving infliximab, three patients receiving etanercept) had more complete drug-induced lupus with systemic manifestations and at least four American Congress of Rheumatology criteria. One patient had central nervous system manifestations. No patients had lupus nephritis. The signs of lupus occurred within a mean of 9 months (range 3-16 months) in patients treated with infliximab and within a mean of 4 months (range 2-5 months) in patients treated with etanercept. In all cases after diagnosis was determined, anti-TNF was stopped and specific treatment introduced in eight patients: two patients received intravenous methylprednisolone, four patients received oral steroids (15-35 mg/day), and two patients received topical steroids. Lupus manifestations abated within a few weeks (median 8 weeks, standard deviation 3-16) in all patients except one with longer-lasting evolution (6 months). At that time, cautious estimations (unpublished data from Schering Plough Inc. and Wyeth Inc.) indicated that about 7700 patients had been exposed to infliximab and 3000 to

  1. Garlic (Allium sativum) stimulates lipopolysaccharide-induced tumor necrosis factor-alpha production from J774A.1 murine macrophages.

    Science.gov (United States)

    Sung, Jessica; Harfouche, Youssef; De La Cruz, Melissa; Zamora, Martha P; Liu, Yan; Rego, James A; Buckley, Nancy E

    2015-02-01

    Garlic (Allium sativum) is known to have many beneficial attributes such as antimicrobial, antiatherosclerotic, antitumorigenetic, and immunomodulatory properties. In the present study, we investigated the effects of an aqueous garlic extract on macrophage cytokine production by challenging the macrophage J774A.1 cell line with the garlic extract in the absence or presence of lipopolysaccharide (LPS) under different conditions. The effect of allicin, the major component of crushed garlic, was also investigated. Using enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction, it was found that garlic and synthetic allicin greatly stimulated tumor necrosis factor-alpha (TNF-α) production in macrophages treated with LPS. The TNF-α secretion levels peaked earlier and were sustained for a longer time in cells treated with garlic and LPS compared with cells treated with LPS alone. Garlic acted in a time-dependent manner. We suggest that garlic, at least partially via its allicin component, acts downstream from LPS to stimulate macrophage TNF-α secretion. © 2014 The Authors. Phytotherapy Research published by John Wiley & Sons, Ltd.

  2. An update on the use of tumor necrosis factor alpha inhibitors in the treatment of ankylosing spondylitis.

    Science.gov (United States)

    Osman, Mohammed S; Maksymowych, Walter P

    2017-02-01

    Ankylosing spondylitis is a chronic immune-mediated disease affecting the sacroiliac joints and the spine manifesting with new bone formation and osteopenia. Over the past decade, tumour necrosis factor alpha (TNF-α) inhibitors (TNFi) have become the cornerstone for therapy in improving functional outcomes, and decreasing disease activity in patients with a marginal benefit from non-steroidal anti-inflammatory (NSAID) therapy. At this time, it remains to be determined whether these agents decrease new bone formation, although some studies have recently suggested that. Areas covered: In this review we discuss the factors that favour a good response to these agents both initially and during maintenance, and some of the more recent studies outlining strategies for dose reduction. Expert commentary: Finally, we discuss the importance of using more objective tools for disease activity, such as magnetic resonance imaging, as a complementary tool for clinical assessments in both predicting responses to treatment but also in selecting patients most suited for targeted therapy.

  3. Alcohol extracts of Echinacea inhibit production of nitric oxide and tumor necrosis factor-alpha by macrophages in vitro.

    Science.gov (United States)

    Zhai, Zili; Haney, Devon; Wu, Lankun; Solco, Avery; Murphy, Patricia A; Wurtele, Eve S; Kohut, Marian L; Cunnick, Joan E

    2007-09-01

    It has been suggested that Echinacea has anti-inflammatory activity in vivo. Nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta are important mediators in the inflammatory response. The effect of alcohol extracts of E. angustifolia (EA), E. pallida (EPA) and E. purpurea (EP) on the production of these inflammatory mediators in both LPS-stimulated RAW 264.7 macrophages in vitro and murine peritoneal exudate cells (PECs) in vivo were investigated. As macrophages produce these inflammatory mediators in response to pathogenic infection, parallel cultures of macrophages were studied for phagocytosis and intracellular killing of Salmonella enterica. EPA and EP in vitro inhibited NO production and TNF-α release in a dose-dependent manner. RAW 264.7 cells treated with EA or EP showed decreased killing over 24 h, although EA enhanced bacterial phagocytosis. Upon bacterial infection, RAW 264.7 cells produce high levels of NO; however, an Echinacea-mediated decrease in NO production was observed. Echinacea alcohol extracts administered orally at 130 mg/kg per day for seven days had a weak effect on NO production and phagocytosis by LPS-stimulated PECs. The results indicated that all Echinacea species significantly decreased inflammatory mediators in vitro, however, only EA and EP reduced bacterial killing. Oral administration of Echinacea alcohol extracts did not adversely affect the development and anti-bacterial function of inflammatory PECs in vivo, however, NO production was decreased during bacterial infection of PECs.

  4. Establishment and evaluation of a transgenic mouse model of arthritis induced by overexpressing human tumor necrosis factor alpha

    Directory of Open Access Journals (Sweden)

    Ge Li

    2016-04-01

    Full Text Available Tumor necrosis factor alpha (TNFα plays a key role in the pathogenesis of rheumatoid arthritis (RA. Blockade of TNFα by monoclonal antibody has been widely used for the therapy of RA since the 1990s; however, its mechanism of efficacy, and potential safety concerns of the treatment are still not fully understood. This study sought to establish a transgenic arthritic mouse model by overexpressing human TNFα (hTNFα and to apply this model as a means to evaluate therapeutic consequences of TNFα inhibitors. The transgenic mouse line (TgTC with FVB background was generated by incorporating 3′-modified hTNFα gene sequences. A progressively erosive polyarthritis developed in the TgTC mice, with many characteristics observed in human rheumatoid arthritis, including polyarticular swelling, impairment of movement, synovial hyperplasia, and cartilage and bone erosion. Gene expression analysis demonstrated that hTNFα is not only expressed in hyperplastic synovial membrane, but also in tissues without lesions, including brain, lung and kidney. Treatment of the TgTC mice with anti-hTNFα monoclonal antibodies (mAb significantly decreased the level of hTNFα in the diseased joint and effectively prevented development of arthritis in a dose-dependent response fashion. Our results indicated that the TgTC mice represent a genetic model which can be used to comprehensively investigate the pathogenesis and therapeutics of TNFα-related diseases.

  5. Requirement of FADD, NEMO, and BAX/BAK for Aberrant Mitochondrial Function in Tumor Necrosis Factor Alpha-Induced Necrosis▿

    Science.gov (United States)

    Irrinki, Krishna M.; Mallilankaraman, Karthik; Thapa, Roshan J.; Chandramoorthy, Harish C.; Smith, Frank J.; Jog, Neelakshi R.; Gandhirajan, Rajesh Kumar; Kelsen, Steven G.; Houser, Steven R.; May, Michael J.; Balachandran, Siddharth; Madesh, Muniswamy

    2011-01-01

    Necroptosis represents a form of alternative programmed cell death that is dependent on the kinase RIP1. RIP1-dependent necroptotic death manifests as increased reactive oxygen species (ROS) production in mitochondria and is accompanied by loss of ATP biogenesis and eventual dissipation of mitochondrial membrane potential. Here, we show that tumor necrosis factor alpha (TNF-α)-induced necroptosis requires the adaptor proteins FADD and NEMO. FADD was found to mediate formation of the TNF-α-induced pronecrotic RIP1-RIP3 kinase complex, whereas the IκB Kinase (IKK) subunit NEMO appears to function downstream of RIP1-RIP3. Interestingly, loss of RelA potentiated TNF-α-dependent necroptosis, indicating that NEMO regulates necroptosis independently of NF-κB. Using both pharmacologic and genetic approaches, we demonstrate that the overexpression of antioxidants alleviates ROS elevation and necroptosis. Finally, elimination of BAX and BAK or overexpression of Bcl-xL protects cells from necroptosis at a later step. These findings provide evidence that mitochondria play an amplifying role in inflammation-induced necroptosis. PMID:21746883

  6. Comparison of the Intravenous and Epidural Administration of Tumor Necrosis Factor-alpha Antagonists in an Experimental Rat Pain Model

    Science.gov (United States)

    Beyaz, Serbülent Gökhan; İnanmaz, Mustafa Erkan; Ergönenç, Tolga; Palabıyık, Onur; Tomak, Yakup; Tuna, Ayça Taş

    2017-01-01

    Introduction: Inflammatory cytokines secreted from the nucleus pulposus are thought to lead to lumbar nerve root compression-like symptoms. Tumor necrosis factor-alpha (TNF-α), an inflammatory cytokine, likely plays an important role in lumbar disc hernia-related leg pain. In this experimental study, we compared the effectiveness of TNF-α antagonists administered through the intravenous or epidural route in lumbar spine pathologies. Materials and Methods: After ethics committee approval had been obtained, 24 Sprague Dawley male rats aged 70–90 days and weighing 250–300 g each were allocated to four groups. In Group I, only the surgical procedure was performed; in Group II, 1 ml of saline solution was administered into the epidural field; in Group III, 10 mg/kg of infliximab was administered into the coccygeal vein; and in Group IV (epidural group), 25 mg of etanercept was administered into the epidural region. Results: When the left leg pull values were analyzed on day 14, whereas there was not a significant difference among the three groups, a decreasing difference was observed in Group IV (P discopathy, TNF-α antagonists administered epidurally led to earlier recovery from radiculopathy-related allodynia compared to intravenous administration. PMID:29284846

  7. Pathophysiological roles of microvascular alterations in pulmonary inflammatory diseases: possible implications of tumor necrosis factor-alpha and CXC chemokines

    Directory of Open Access Journals (Sweden)

    Kanami Orihara

    2008-10-01

    Full Text Available Kanami Orihara, Akio MatsudaDepartment of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, JapanAbstract: Chronic obstructive pulmonary disease (COPD and bronchial asthma are common respiratory diseases that are caused by chronic infl ammation of the airways. Although these diseases are mediated by substantially distinct immunological reactions, especially in mild cases, they both show increased numbers of neutrophils, increased production of tumor necrosis factor-alpha (TNF-α and poor responses to corticosteroids, particularly in patients with severe diseases. These immunological alterations may contribute strongly to airway structural changes, commonly referred to as airway remodeling. Microvascular alterations, a component of airway remodeling and caused by chronic inflammation, are observed and appear to be clinically involved in both diseases. It has been well established that vascular endothelial growth factor (VEGF plays important roles in the airway microvascular alterations in mild and moderate cases of both diseases, but any role that VEGF might play in severe cases of these diseases remains unclear. Here, we review recent research findings, including our own data, and discuss the possibility that TNF-α and its associated CXC chemokines play roles in microvascular alterations that are even more crucial than those of VEGF in patients with severe COPD or asthma.Keywords: TNF-α, CXC chemokines, corticosteroid, pulmonary microvessels, COPD, asthma

  8. Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis

    Science.gov (United States)

    Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Tatsuki, Yoshihiko; Yano, Toshiro; Yoshinari, Toru; Abe, Tohru; Koike, Takao

    2011-01-01

    Objectives To investigate the possible role of baseline plasma tumour necrosis factor alpha levels (baseline-TNF) on the clinical response to infliximab in patients with rheumatoid arthritis (RA). Methods Patients with RA refractory to methotrexate received 3, 6, or 10 mg/kg of infliximab every 8 weeks, in a randomised, double-blind manner: the RISING study. Clinical response (disease activity score in 28 joints based on C-reactive protein or American College of Rheumatology core set) at week 54 and serum infliximab levels were compared in three patient groups with low, intermediate, or high baseline-TNF (TNF-low, TNF-int, or TNF-high). Results In TNF-low patients, the clinical response to different doses of infliximab was comparable, whereas TNF-int patients exhibited a dose-dependent trend. In contrast, TNF-high patients (approximately 13% of the total patients) had a clinical response to 10 mg/kg significantly better than the response to 3 and 6 mg/kg of infliximab. In TNF-high patients, the median trough serum levels of infliximab were below the detection limit (infliximab in patients with a high baseline-TNF. A higher dose of infliximab may be necessary in these patients, whereas lower doses of infliximab are sufficient for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab. PMID:21478189

  9. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6...

  10. [Role of serum leptin and tumor necrosis factor-alpha in malnutrition of male chronic obstructive pulmonary disease patients].

    Science.gov (United States)

    Yang, Yi-meng; Sun, Tie-ying; Liu, Xin-min

    2005-12-18

    To explore the function of serum leptin in COPD patients with malnutrition, and to investigate the relationship between leptin and TNF-alpha. A total of 81 subjects (47 COPD patients and 34 control subjects) participated in this study. The 47 COPD patients were divided into 2 groups: group COPD I (patients without malnutrition during stable disease, n=29), group COPDII (patients with malnutrition during stable disease, n=18). To eliminate the effect of sex differences, all the patients and controls were male. Body mass index (BMI), percent ideal body weight (IBWå), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference(MAMC),serum leptin and tumor necrosis factor-alpha(TNF-alpha) levels, serum prealbumin (PA), serum transferrin (TF), serum albumin(Alb),total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure(MIP)and maximal expiration pressure(MEP)were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analysed. (1) Serum leptin levels were significantly lower in group COPDII (4.07+/-3.42 microg/L) than in group COPD I (9.72+/-6.67 microg/L) and controls (8.21+/- 5.41 microg/L, PCOPD I (7.25+/- 2.08 ng/L). (3) There was no significant correlation between leptin and TNF-alpha in any group. Leptin was not involved in anorexia and weight loss of COPD patients. There was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

  11. Pentoxifylline inhibits tumor necrosis factor-alpha (TNF alpha)-induced T-lymphoma cell adhesion to endothelioma cells.

    Science.gov (United States)

    Weiss, J M; Vanscheidt, W; Pilarski, K A; Weyl, A; Peschen, M; Schöpf, E; Vestweber, D; Simon, J C

    1995-05-01

    Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms. Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-alpha (TNF alpha), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNF alpha, but not of untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent (10(-5)-10(-3) M) fashion. Selective incubation of either endothelioma cells or T-lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNF alpha stimulation. We questioned whether pentoxifylline suppressed T-lymphoma cell/endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNF alpha-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.

  12. Alteration of serum tumor necrosis factor-alpha level in gestational diabetes mellitus and correlation with insulin resistance

    International Nuclear Information System (INIS)

    Zou Gang; Li Cuiyin; Shao Hao; Lu Zeyuan; Lai Liping; Liu Lan; Hu Xiaorong

    2009-01-01

    Objective: To explore the dynamic of tumor necrosis factor-alpha (TNF-α)and its correlation with insulin resistance (IR)during different stages of gestational diabetes mellitus (GDM). Methods: Thirty-two subjects with GDM and 31 cases of normal pregnant women nonnal glucose tolerance, NGT were enrolled in the study, serum TNF-α and insulin were determined by radioimmunoassay. The plasma glucose was measured by using glucose oxidase. Tests repeated for each group according different stages of prenatal 25-28 weeks, 29-32 weeks, 37-38 weeks and postpartum 6-8 weeks. IR was assessed by the homeostasis model of assessment for insulin resistance index (HOMA-IR). Results: (1)Serum TNF-α levels in CDM and NGT group rose with gestational age, and both significantly decreased at postpartum. (2) Serum TNF-α levels in GDM of above-mentioned four stages respectively were (7.05±0.67) ng/L, (7.11± 0.75) ng/L, (7.36±0.79) ng/L, (5.46±0.37) ng/L respectively. All significantly increased than those in the same stage group (t=7.81, 7.05, 7.15, P<0.01). (3) Maternal serum TNF-α levels were in positive correlation with HOMA-IR in GDM (r=0.571, P<0.05). Conclusions: Serum TNF-α levels in GDM rose with gestational age, but significantly decreased at postpartum. The dynamic changes of serum TNF-α contribute to occurrence of insulin resistance. (authors)

  13. Quantitative assessment of the influence of tumor necrosis factor alpha polymorphism with gastritis and gastric cancer risk.

    Science.gov (United States)

    Li, Ming; Wang, Yinping; Gu, Yahong

    2014-02-01

    Tumor necrosis factor alpha (TNFA) is an important molecule in inflammatory, infectious, and tumoral processes. Inflammation is one of the early phases in the development of gastric cancer (GC). Therefore, several studies have examined the association of polymorphism in TNFA with gastritis and GC risk. A functional polymorphism, -308G>A (rs1800629), which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. To date, a number of studies have been carried out to investigate the relationship between the polymorphism and gastritis or GC susceptibility, but the results were conflicting. To investigate this inconsistency, we performed a meta-analysis of 36 studies for TNFA -308G>A polymorphism to evaluate the effect of TNFA on genetic susceptibility for gastritis and GC. An overall random-effects per-allele odds ratio of 1.16 (95 % confidence interval 1.04-1.29, P = 0.008) was found for the polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians, whereas no significant associations were found among East Asians and other ethnic populations. No associations between the polymorphism and gastritis were observed. In addition, our data indicate that TNFA is involved in GC susceptibility and confers its effect primarily in diffuse type of tumors. Besides, -308G>A polymorphism was found to be significantly associated with both cardiac and noncardiac tumors. This meta-analysis demonstrated that the TNFA -308G>A polymorphism is a risk factor for developing GC, but the associations vary in different ethnic populations.

  14. Anti-tumor necrosis factor-alpha-loaded microspheres as a prospective novel treatment for Crohn's disease fistulae.

    Science.gov (United States)

    Foong, Keen Shawn; Patel, Rishni; Forbes, Alastair; Day, Richard M

    2010-10-01

    Antibodies to tumor necrosis factor alpha (TNF-α) have been successful in treating perianal fistulae in Crohn's disease, but current modes of delivery are limited. Microspheres are currently being assessed as scaffolds for tissue engineering and drug delivery devices. The aim of this study was to produce anti-TNF-α antibody-encapsulated microspheres using thermally induced phase separation (TIPS) and to characterize their behavior. Anti-TNF-α antibody was encapsulated into the microspheres (100 mg infliximab/g poly[lactide-co-glycolide] w/w) using a novel technique combining a vibration encapsulator unit with a TIPS process, using either lyophilized particulate antibody or an aqueous solution of antibody. Microspheres were incubated in phosphate-buffered saline for collection of supernatant and assessment of degradation. The amount and biological activity of the encapsulated antibody released from the microspheres was assessed by enzyme-linked immunosorbent assay and its ability to neutralize recombinant human (rh)TNF-α in vitro with a cytotoxicity assay. An in vitro wound scratch assay was used to assess the effect of released antibody on fibroblast migration. Ultrastructural characteristics of the different microspheres were characterized by scanning electron microscopy. Highly porous microspheres released anti-TNF-α antibody under zero-order kinetics and inhibited the cytotoxic activity of rhTNF-α, producing a significant increase in cell viability compared with cells treated with rhTNF-α alone. This effect was most pronounced with microspheres fabricated by blending lyophilized particulate anti-TNF-α antibody into the polymer solution, which also significantly reduced the release of lactate dehydrogenase. Anti-TNF-α antibody encapsulated into highly porous microspheres was released in a controlled manner and exhibited biological activity against TNF-α. The technique used to produce TIPS microspheres is rapid and provides high encapsulation efficiency

  15. Preliminary characterisation of tumor necrosis factor alpha and interleukin-10 responses to Chlamydia pecorum infection in the koala (Phascolarctos cinereus.

    Directory of Open Access Journals (Sweden)

    Marina Mathew

    Full Text Available Debilitating infectious diseases caused by Chlamydia are major contributors to the decline of Australia's iconic native marsupial species, the koala (Phascolarctos cinereus. An understanding of koala chlamydial disease pathogenesis and the development of effective strategies to control infections continue to be hindered by an almost complete lack of species-specific immunological reagents. The cell-mediated immune response has been shown to play an influential role in the response to chlamydial infection in other hosts. The objective of this study, hence, was to provide preliminary data on the role of two key cytokines, pro-inflammatory tumour necrosis factor alpha (TNFα and anti-inflammatory interleukin 10 (IL10, in the koala Chlamydia pecorum response. Utilising sequence homology between the cytokine sequences obtained from several recently sequenced marsupial genomes, this report describes the first mRNA sequences of any koala cytokine and the development of koala specific TNFα and IL10 real-time PCR assays to measure the expression of these genes from koala samples. In preliminary studies comparing wild koalas with overt chlamydial disease, previous evidence of C. pecorum infection or no signs of C. pecorum infection, we revealed strong but variable expression of TNFα and IL10 in wild koalas with current signs of chlamydiosis. The description of these assays and the preliminary data on the cell-mediated immune response of koalas to chlamydial infection paves the way for future studies characterising the koala immune response to a range of its pathogens while providing reagents to assist with measuring the efficacy of ongoing attempts to develop a koala chlamydial vaccine.

  16. Preliminary characterisation of tumor necrosis factor alpha and interleukin-10 responses to Chlamydia pecorum infection in the koala (Phascolarctos cinereus).

    Science.gov (United States)

    Mathew, Marina; Beagley, Kenneth W; Timms, Peter; Polkinghorne, Adam

    2013-01-01

    Debilitating infectious diseases caused by Chlamydia are major contributors to the decline of Australia's iconic native marsupial species, the koala (Phascolarctos cinereus). An understanding of koala chlamydial disease pathogenesis and the development of effective strategies to control infections continue to be hindered by an almost complete lack of species-specific immunological reagents. The cell-mediated immune response has been shown to play an influential role in the response to chlamydial infection in other hosts. The objective of this study, hence, was to provide preliminary data on the role of two key cytokines, pro-inflammatory tumour necrosis factor alpha (TNFα) and anti-inflammatory interleukin 10 (IL10), in the koala Chlamydia pecorum response. Utilising sequence homology between the cytokine sequences obtained from several recently sequenced marsupial genomes, this report describes the first mRNA sequences of any koala cytokine and the development of koala specific TNFα and IL10 real-time PCR assays to measure the expression of these genes from koala samples. In preliminary studies comparing wild koalas with overt chlamydial disease, previous evidence of C. pecorum infection or no signs of C. pecorum infection, we revealed strong but variable expression of TNFα and IL10 in wild koalas with current signs of chlamydiosis. The description of these assays and the preliminary data on the cell-mediated immune response of koalas to chlamydial infection paves the way for future studies characterising the koala immune response to a range of its pathogens while providing reagents to assist with measuring the efficacy of ongoing attempts to develop a koala chlamydial vaccine.

  17. The expression of tumor necrosis factor-alpha, its receptors and steroidogenic acute regulatory protein during corpus luteum regression

    Directory of Open Access Journals (Sweden)

    Arfuso Frank

    2008-11-01

    Full Text Available Abstract Background Corpus luteum (CL regression is known to occur as two parts; functional regression when steroidogenesis declines and structural regression when apoptosis is induced. Previous studies suggest this process occurs by the production of luteolytic factors, such as tumour necrosis factor-alpha (TNF-alpha. Methods We examined TNF-alpha, TNF-alpha receptors (TNFR1 and 2 and steroidogenic acute regulatory (StAR protein expression during CL regression in albino Wistar rats. CL from Days 16 and 22 of pregnancy and Day 3 post-partum were examined, in addition CL from Day 16 of pregnancy were cultured in vitro to induce apoptosis. mRNA was quantitated by kinetic RT-PCR and protein expression examined by immunohistochemistry and Western blot analyses. Results TNF-alpha mRNA increased on Day 3 post-partum. TNFR were immunolocalized to luteal cells, and an increase in TNFR2 mRNA observed on Day 3 post-partum whilst no change was detected in TNFR1 mRNA relative to Day 16. StAR protein decreased on Day 3 post-partum and following trophic withdrawal but no change was observed following exogenous TNF-alpha treatment. StAR mRNA decreased on Day 3 post-partum; however, it increased following trophic withdrawal and TNF-alpha treatment in vitro. Conclusion These results demonstrate the existence of TNFR1 and TNFR2 in rat CL and suggest the involvement of TNF-alpha in rat CL regression following parturition. Furthermore, decreased StAR expression over the same time points was consistent with the functional regression of the CL.

  18. Ethanol increases tumor necrosis factor-alpha receptor-1 (TNF-R1) levels in hepatic, intestinal, and cardiac cells.

    Science.gov (United States)

    Rodriguez, Diego A; Moncada, Claudio; Núñez, Marco T; Lavandero, Sergio; Ponnappa, Biddanda C; Israel, Yedy

    2004-05-01

    Chronic ethanol consumption leads to cell injury in virtually every tissue. Tumor necrosis factor-alpha (TNF-alpha) constitutes a major factor in the development of alcohol-induced liver injury. In alcohol-dependent subjects, elevated levels of plasma TNF-alpha are strongly predictive of mortality. Binding of TNF-alpha to TNF-alpha receptor-1 (TNF-R1) activates death domain pathways, leading to necrosis and apoptosis in most tissues, and it also increases the expression of intercellular adhesion molecules (i.e., ICAM-1), which promote inflammation. We determined whether ethanol exposure leads to increases in cellular TNF-R1. We incubated HepG2 human hepatoma cells and H4-II-E-C3 rat hepatoma cells with 25, 50, and 100 mM ethanol for various intervals of time up to 48 h. Human colonic adenocarcinoma cells (Caco-2 cells) and neonatal rat primary cardiomyocytes were also incubated with different concentrations of ethanol. Levels of TNF-R1 were measured either by a sandwich enzyme-linked immunosorbent assay (ELISA) method or by determining the extracellular transmembrane domain of TNF-R1 by an intact-cell ELISA method. Ethanol exposure for 48 h increased TNF-R1 levels in human hepatoma cells in a dose-dependent manner. Levels increased significantly by 164% at 50 mM and by 240% at 100 mM ethanol. Effects were time dependent and did not reach a plateau at 48 h. Similar increases in TNF-R1 were also observed in rat hepatoma cells (90% at 50 mM and 230% at 100 mM ethanol). Under similar conditions, Caco-2 cells showed a significant 80% increase in TNF-R1 levels at 200 mM ethanol, a concentration found in intestine. Neonatal rat primary cardiomyocytes showed TNF-R1 increases of 36% at 50 mM and 44% at 100 mM ethanol. These results indicate that exposure of different cell types to pharmacologic concentrations of ethanol increases TNF-R1 levels and may augment TNF-alpha-mediated cell injury in different tissues.

  19. Circulating levels of tumor necrosis factor-alpha receptor 2 are increased in heart failure with preserved ejection fraction relative to heart failure with reduced ejection fraction: evidence for a divergence in pathophysiology.

    Directory of Open Access Journals (Sweden)

    Brendan N Putko

    Full Text Available Various pathways have been implicated in the pathogenesis of heart failure (HF with preserved ejection fraction (HFPEF. Inflammation in response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role in HFPEF as compared to HF with reduced ejection fraction (HFREF.This study investigated inflammation mediated by the tumor necrosis factor-alpha (TNFα axis in community-based cohorts of HFPEF patients (n = 100, HFREF patients (n = 100 and healthy controls (n = 50. Enzyme-linked immunosorbent assays were used to investigate levels of TNFα, its two receptors (TNFR1 and TNFR2, and a non-TNFα cytokine, interleukin-6 (IL-6, in plasma derived from peripheral blood samples. Plasma levels of TNFα and TNFR1 were significantly elevated in HFPEF relative to controls, while levels of TNFR2 were significantly higher in HFPEF than both controls and HFREF. TNFα, TNFR1 and TNFR2 were each significantly associated with at least two of the following: age, estimated glomerular filtration rate, hypertension, diabetes, smoking, peripheral vascular disease or history of atrial fibrillation. TNFR2 levels were also significantly associated with increasing grade of diastolic dysfunction and severity of symptoms in HFPEF.Inflammation mediated through TNFα and its receptors, TNFR1 and TNFR2, may represent an important component of a comorbidity-induced inflammatory response that partially drives the pathophysiology of HFPEF.

  20. Effects of MS-8209, an Amphotericin B Derivative, on Tumor Necrosis Factor Alpha Synthesis and Human Immunodeficiency Virus Replication in Macrophages

    OpenAIRE

    Clayette, Pascal; Martin, Marc; Beringue, Vincent; Dereuddre-Bosquet, Nathalie; Adjou, Karim T.; Seman, Michel; Dormont, Dominique

    2000-01-01

    Amphotericin B derivatives, such as MS-8209, have been evaluated as a therapeutic approach to human immunodeficiency virus (HIV) infection. We show that MS-8209, like amphotericin B, increases tumor necrosis factor alpha (TNF-α) mRNA expression and TNF-α production and consequently HIV replication in human macrophages. These effects confirm the pharmacological risk associated with the administration of amphotericin B or its derivatives to HIV-infected patients.

  1. Effects of MS-8209, an amphotericin B derivative, on tumor necrosis factor alpha synthesis and human immunodeficiency virus replication in macrophages.

    Science.gov (United States)

    Clayette, P; Martin, M; Beringue, V; Dereuddre-Bosquet, N; Adjou, K T; Seman, M; Dormont, D

    2000-02-01

    Amphotericin B derivatives, such as MS-8209, have been evaluated as a therapeutic approach to human immunodeficiency virus (HIV) infection. We show that MS-8209, like amphotericin B, increases tumor necrosis factor alpha (TNF-alpha) mRNA expression and TNF-alpha production and consequently HIV replication in human macrophages. These effects confirm the pharmacological risk associated with the administration of amphotericin B or its derivatives to HIV-infected patients.

  2. Intervertebral disc cells produce tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model.

    Science.gov (United States)

    Yoshida, Masakazu; Nakamura, Takafumi; Sei, Akira; Kikuchi, Taro; Takagi, Katsumasa; Matsukawa, Akihiro

    2005-01-01

    A new hernia model that simulates human disc herniations was developed in rabbits. The herniated discs were examined by gross appearance and histology and production of tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 was investigated. To clarify the early mechanism of spontaneous herniated disc resorption. Macrophage infiltration in herniated discs is essential for disc resorption. However, surgically removed human herniated disc tissues and existing animal hernia models are not suitable for analyzing the mechanism of macrophage infiltration. Recently, we have demonstrated that intervertebral disc cells are capable of producing monocyte chemoattractant protein-1, a potent macrophage chemoattractant, after stimulation with tumor necrosis factor alpha and interleukin-1beta. Intervertebral disc herniations were surgically developed in rabbits using a new technique. The herniated discs were excised at appropriate time intervals after the surgery, and the size and histologic findings were examined. Expressions of tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 in herniated discs were investigated immunohistochemically. A new rabbit model of disc herniation was established. The herniated discs spontaneously reduced in size by 12 weeks postsurgery. Infiltrating cells, mainly composed of macrophages, were observed from day 3. Immunohistochemically, intervertebral disc cells in the herniated discs produced tumor necrosis factor alpha and interleukin-1beta on day 1, followed by monocyte chemoattractant protein-1 on day 3. The new hernia model appears to be very useful for studying herniated disc resorption. Intervertebral disc cells may produce inflammatory cytokines/chemokine immediately after the onset of disc herniation, possibly triggering subsequent macrophage infiltration that leads to disc resorption.

  3. Evaluation of Cucurbita maxima extract against scopolamine-induced amnesia in rats: implication of tumour necrosis factor alpha.

    Science.gov (United States)

    Jawaid, Talha; Shakya, Ashok K; Siddiqui, Hefazat Hussain; Kamal, Mehnaz

    2014-01-01

    Cucurbita maxima (CM) seed oil is commonly used in Indian folk medicine to treat various ailments. We have investigated the effect of CM seed oil on memory impairment induced by scopolamine in rats. Male adult Wistar rats were administered scopolamine 1 mg/kg body weight, i.p. or 1.25 mg/kg body weight, s.c. to induce memory impairment. The nootropic agent piracetam 100 mg/kg body weight, i.p. and CM seed oil 100 and 200 mg/kg body weight, p.o. were administered daily for five consecutive days. The memory function was evaluated in the Morris water maze (MWM) test, the social recognition test (SRT), the elevated plus maze (EPM) test, and the pole climbing test (PCT). Acetylcholinesterase (AChE) activity and oxidative stress parameters were estimated in the cortex, hippocampus, and cerebellum of the brains after completion of the behavioural studies. The effects of scopolamine on the levels of the tumour necrosis factor alpha (TNF-α) transcript were also investigated. Scopolamine caused memory impairment in all the behavioural paradigms along with a significant increase in the AChE activity and oxidative stress in the brain. Scopolamine also caused a significant increase in the expression of TNF-α in the hippocampus. CM seed oil exhibited antiamnesic activity as indicated by a significant reduction in the latency time in the MWM test and decreased social interaction during trial 2 in the SRT. Further, treatment with CM seed oil significantly decreased the AChE activity and malondialdehyde levels and increased the glutathione level in brain regions. CM seed oil also significantly decreased the expression of TNF-α in the hippocampus. The effect of CM seed oil on behavioural and biochemical parameters was comparable to that observed in rats treated with piracetam. These results indicate that CM seed oil may exert antiamnesic activity which may be attributed to the inhibition of AChE and inflammation as well as its antioxidant activity in the brain.

  4. Working life and physical activity in ankylosing spondylitis pre and post anti-tumor necrosis factor-alpha therapy.

    Science.gov (United States)

    Prince, David S; McGuigan, Louis E; McGirr, Ellen E

    2014-02-01

    To assess effects of ankylosing spondylitis (AS) on working life and physical activity in Australia; to quantify changes in working life and physical activity that occur after anti-tumor necrosis factor-alpha (TNF-α) treatment; and to assess efficacy of anti-TNF-α therapy for AS in an Australian context. This is a multi-centre observational study of people with AS on anti-TNF-α therapy. All participants satisfied the New York Modified Criteria and had active and refractory disease at anti-TNF-α therapy commencement. Participation involved a standardized interview, a metrology assessment, assessment of disease remission and medical record review. Interviews and patients' records were used to compare working life (employment, sick leave and productivity) and physical activity (participation rate, hours/week, and physical intensity) between the pre-AS, post-AS and post-anti-TNF-α therapy periods. Fifty-two patients took part. Participants were on average 44.8 years old, predominately male (86.5%) and had been on anti-TNF-α therapy for 29 months; 39% were in partial remission and 75% had 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Responders to anti-TNF-α therapy were 10.5 years younger than non-responders (P = 0.004). Post-anti-TNF-α therapy participants gained 6.6 h/week of work (P = 0.02), and productivity improved 31% (P treatment. Physical activity participation increased from 71% to 85% (P = 0.039) and activity intensity increased by 33% (P = 0.002) post-treatment. Participants gained 1.8 h/week of sport (P = 0.001) and 2.2 h/week of recreational physical activity (P Treatment with anti-TNF-α therapy results in significant improvement in these parameters. © 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  5. Association of Polymorphism Harbored by Tumor Necrosis Factor Alpha Gene and Sex of Calf with Lactation Performance in Cattle

    Directory of Open Access Journals (Sweden)

    N. S. Yudin

    2013-10-01

    Full Text Available In a majority of mammals, male infants have heavier body mass and grow faster than female infants. Accordingly, male offspring nursing requires a much greater maternal energy contribution to lactation. It is possible that the maternal-fetal immunoendocrine dialog plays an important role in female preparation for lactation during pregnancy. Immune system genes are an integral part of gene regulatory networks in lactation and tumor necrosis factor alpha (TNFα is a proinflammatory cytokine that also plays an important role in normal mammary gland development. The aim of this study was to evaluate the influence of the sex of calf and/or the -824A/G polymorphism in the promoter region of TNFα gene on milk performance traits in Black Pied cattle over the course of lactation. We also studied the allele frequency differences of -824A/G variants across several cattle breeds, which were bred in different climatic conditions. The G allele frequency decreased gradually over the course of lactation events in the Black Pied dairy cattle because of a higher culling rate of cows with the G/G genotype (p<0.001. In contrast to the genotypes A/A and A/G, cows with G/G genotype showed significant variability of milk and milk fat yield subject to sex of delivered calf. Milk yield and milk fat yield were significantly higher in the case of birth of a bull calf than with a heifer calf (p<0.03. The G allele frequency varies from 48% to 58% in Grey Ukrainian and Black Pied cattle to 77% in aboriginal Yakut cattle. Our results suggest that the TNFα -824A/G gene polymorphism may have an influence on the reproductive efforts of cows over the course of lactation events depending on the sex of progeny. Allocation of resources according to sex of the calf allows optimizing the energy cost of lactation. This may be a probable reason for high G allele frequency in Yakut cattle breeding in extreme environmental conditions. Similarly, the dramatic fall in milk production after

  6. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    Science.gov (United States)

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  7. The role of serum leptin and tumor necrosis factor-alpha in malnutrition of male chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Yang, Yi-meng; Sun, Tie-ying; Liu, Xin-min

    2006-04-20

    Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha. Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed. Serum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9

  8. Influence of butter and of corn, coconut and fish oils on the effects of recombinant human tumour necrosis factor-alpha in rats.

    Science.gov (United States)

    Mulrooney, H M; Grimble, R F

    1993-01-01

    1. Tumour necrosis factor-alpha is produced in response to inflammatory stimuli. Fish oil can suppress the production and actions of cytokines. Little information is available on the effects of other fats on cytokine biology. We compared the effects of fats, with a wide range of fatty acid characteristics, on the effects of tumour necrosis factor-alpha on protein and zinc metabolism in rats. 2. Weanling rats were fed for 8 weeks on diets containing 10% fat in the form of corn, fish or coconut oils or butter before an intraperitoneal injection of recombinant human tumour necrosis factor-alpha was given. Measurements were made 24h after the injection. 3. In rats fed corn oil, food intake was reduced by 62% and rates of protein synthesis were increased by 86, 32 and 39% in the liver, lung and kidney, respectively. Zinc concentrations increased by 23% in the liver but decreased by 10% in the kidney. Plasma caeruloplasmin and complement C3 levels increased by 25% and 28%, respectively, and plasma albumin level decreased by 24%. 4. Fish oil prevented the increase in hepatic protein synthesis and changed the response of protein synthesis in lung and kidney to a decrease. Changes in hepatic and renal zinc concentrations were prevented. The response of the plasma caeruloplasmin level was unaltered but those of the plasma complement C3 and albumin concentrations were prevented. 5. Coconut oil and butter, although similarly low in linoleic acid, differed in their modulatory effects. With the exception of the rise in the plasma complement C3 concentration, all responses were prevented or greatly inhibited in rats fed butter.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Polymorphisms in the tumor necrosis factor-alpha gene at position -308 and the inducible 70 kd heat shock protein gene at position +1267 in multifetal pregnancies and preterm premature rupture of fetal membranes.

    Science.gov (United States)

    Kalish, Robin B; Vardhana, Santosh; Gupta, Meruka; Perni, Sriram C; Chasen, Stephen T; Witkin, Steven S

    2004-10-01

    The purpose of this study was to determine the relationship between preterm premature rupture of membranes, tumor necrosis factor-alpha, and heat shock protein-70 gene polymorphisms in multifetal gestations. Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested for single nucleotide polymorphisms at position -308 of the tumor necrosis factor-alpha gene and +1267 of the heat shock protein-70 gene. Pregnancy outcome data were obtained subsequently. Tumor necrosis factor-alpha allele 2 carriage by the first-born occurred in 10 of 27 pregnancies (37.0%) that resulted in preterm premature rupture of membranes compared with 6 of 67 pregnancies (9.0%) without preterm premature rupture of membranes ( P = .002). The allele frequency of tumor necrosis factor-alpha allele 2 and heat shock protein-70 allele 2 in the first born was higher in pregnancies that were complicated by preterm premature rupture of membranes (18.5% vs 4.5%; P = .003; and 57.7% vs 41.3%; P = .04, respectively). There was no relationship between tumor necrosis factor-alpha allele 2 or heat shock protein-70 allele 2 carriage by the second fetus or mother and preterm premature rupture of membranes. Tumor necrosis factor-alpha allele 2 and/or heat shock protein-70 allele 2 carriage by the first-born fetus is associated with preterm premature rupture of membranes in multifetal pregnancies.

  10. Forward and Reverse Signaling Mediated by Transmembrane Tumor Necrosis Factor-Alpha and TNF Receptor 2: Potential Roles in an Immunosuppressive Tumor Microenvironment

    OpenAIRE

    Qu, Yang; Zhao, Gang; Li, Hui

    2017-01-01

    Tumor necrosis factor-alpha (TNF-α) is a pleiotropic inflammatory cytokine produced mainly by activated macrophages, lymphocytes and other cell types. Two distinct forms of TNF-α have been identified: soluble TNF-α (sTNF-α) and transmembrane TNF-α (mTNF-α). mTNF-α, which is the precursor of sTNF-α, can be cleaved by the TNF-α converting enzyme (TACE) and is released as sTNF-α. sTNF-α binds primarily to TNF receptor 1 (TNFR1) and plays an important role in the inflammatory immune response, whe...

  11. Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

    DEFF Research Database (Denmark)

    Andreassen, B. U.; Pærregaard, Anders; Michaelsen, Kim F.

    2008-01-01

    To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels...... during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days -3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy...

  12. Systemic administration of an anti-tumor necrosis factor-alpha monoclonal antibody protects against endotoxin-induced uveitis in rats

    OpenAIRE

    Ge, Qingman; Wang, Shaocheng; Zheng, Yuezhong

    2016-01-01

    Objective: This study was to evaluate the effect of systemic injection of an anti-tumor necrosis factor alpha (TNF-?) monoclonal antibody (mAb) on endotoxin-induced uveitis (EIU). Materials and Methods: Fifty-six male Wistar rats (6?8 weeks old) were randomly divided into three groups: EIU, anti-TNF-? mAb + EIU, and control. EIU was induced by injecting Escherichia coli O55:B5 lipopolysaccharide (LPS) into the hind footpad of the rats (150 ?g/rat). The anti-TNF-? mAb (1 ?g/kg) was administrat...

  13. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Science.gov (United States)

    Vázquez-Del Mercado, Mónica; Nuñez-Atahualpa, Lourdes; Figueroa-Sánchez, Mauricio; Gómez-Bañuelos, Eduardo; Rocha-Muñoz, Alberto Daniel; Martín-Márquez, Beatriz Teresita; Martínez-García, Erika Aurora; Macias-Reyes, Héctor; Gamez-Nava, Jorge Ivan; Navarro-Hernandez, Rosa Elena; Nuñez-Atahualpa, María Alejandra; Andrade-Garduño, Javier

    2015-01-01

    The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. PMID:25821796

  14. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Mónica Vázquez-Del Mercado

    2015-01-01

    Full Text Available The main cause of death in rheumatoid arthritis (RA is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP antibody levels with increased carotid intima-media thickness (cIMT in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC were studied. All groups were assessed for atherogenic index of plasma (AIP and cIMT. Anti-CCP, C-reactive protein (CRP, and levels of tumor necrosis factor alpha (TNFα and interleukin-6 (IL-6 were measured by enzyme-linked immunosorbent assay (ELISA. Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P<0.001. Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P<0.01, and lower levels of high density lipoprotein cholesterol (HDL-c (P=0.02. The cIMT correlated with levels of anti-CCP (r=0.513, P=0.001, CRP (r=0.799, P<0.001, TNFα (r=0.642, P=0.001, and IL-6 (r=0.751, P<0.001. In multiple regression analysis, cIMT was associated with CRP (P<0.001 and anti-CCP levels (P=0.03. Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.

  15. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma

    NARCIS (Netherlands)

    Wenzel, Sally E.; Barnes, Peter J.; Bleecker, Eugene R.; Bousquet, Jean; Busse, William; Dahlén, Sven-Erik; Holgate, Stephen T.; Meyers, Deborah A.; Rabe, Klaus F.; Antczak, Adam; Baker, James; Horvath, Ildiko; Mark, Zsuzsanna; Bernstein, David; Kerwin, Edward; Schlenker-Herceg, Rozsa; Lo, Kim Hung; Watt, Rosemary; Barnathan, Elliot S.; Chanez, Pascal; Chanez, P.; Tunon-de-Lara, M.; Antczak, A.; Pierzchala, W.; Bukowczan, Z.; Trawinska, E.; Baker, J.; Wenzel, S. E.; Katial, R.; Bernstein, D.; Kerwin, E.; Bensch, G.; Castro, M.; Noonan, M.; Nayak, A.; Chupp, G.; Kline, J.; Busse, W.; Kavuru, M. S.; Lang, D.; Wolfe, R.; Baughman, R.; Korenblat, P.; Mansfield, L.; Bleecker, E.; Lisberg, E.; Liu, M.; Panettieri, R.; Spangenthal, S.; Bel, E. H.

    2009-01-01

    RATIONALE: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. OBJECTIVES: To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma.

  16. Activity and tissue-specific expression of lipases and tumor-necrosis factor alpha in lean and obese cats.

    NARCIS (Netherlands)

    Hoenig, M.; McGoldrick, J.B.; Beer, M. de; Demacker, P.N.M.; Ferguson, D.C.

    2006-01-01

    Post-heparin plasma activity of lipoprotein lipase (LPL) and hepatic lipase (HL), and fat and muscle activity of LPL were measured in neutered lean and obese cats. Lipoprotein lipase, hormone-sensitive lipase (HSL), and tumor necrosis factor a (TNF) mRNA were measured in muscle and fat tissue with

  17. The effect of chronic periodontitis on serum levels of tumor necrosis factor-alpha in Alzheimer disease.

    Science.gov (United States)

    Farhad, Shirin Zahra; Amini, Shahram; Khalilian, Amir; Barekatain, Majid; Mafi, Morvarid; Barekatain, Mehrdad; Rafei, Ehsan

    2014-09-01

    Despite the outbreak in dental science, oral and dental complications in Alzheimer are of the unsolved problems. It is assumed that tumor necrosis factor-α, which is a key factor in Alzheimer, has a relation with periodontal complications in patients with Alzheimer disease. The present study evaluated the effect of chronic periodontitis on serum levels of tumor necrosis factor-α in Alzheimer disease. This case-control study was performed on 80 patients with Alzheimer disease seeking medical care at Nour Hospital, Isfahan, Iran. Eighty patients with Alzheimer disease between 40 and 70 years old attended this study. Forty had chronic periodontitis (case group), and 40 patients had healthy periodontium (control group). Blood sample was taken, and serum levels of tumor necrosis factor-α were measured by means of an ELISA Reader device. Independent T-Test was used to analyze data, and P patients with Alzheimer and periodontitis was approximately three folds higher than the patients only with Alzheimer, and this difference was statistically significant (P patient with Alzheimer and chronic periodontitis and patients with Alzheimer disease and healthy periodontium. Tumor necrosis factor-α level in serum may act as a diagnostic marker of periodontal disease in patients with Alzheimer disease.

  18. Maturation of human dendritic cells by monocyte-conditioned medium is dependent upon trace amounts of lipopolysaccharide inducing tumour necrosis factor alpha

    DEFF Research Database (Denmark)

    Nersting, Jacob; Svenson, Morten; Andersen, Vagn

    2003-01-01

    We investigated the ability of monocyte-conditioned medium (MCM), generated by monocytes cultured on plastic-immobilised immunoglobulin, to stimulate maturation of human monocyte-derived dendritic cells (DC). Earlier reports suggest that MCM is a strong inducer of irreversible DC maturation......, whereas we find, that adding a small amount of lipopolysaccharide (LPS) to the MCM-generating cultures is required for the production of a DC-stimulatory MCM. Moreover, compared with addition of LPS directly to the DC cultures, stimulation via MCM cultures increases by several fold the DC......-stimulatory potency of LPS. Maturation by this procedure is mediated mainly by tumour necrosis factor alpha secreted from monocytes during the medium-conditioning period....

  19. A low concentration of ethanol reduces the chemiluminescence of human granulocytes and monocytes but not the tumor necrosis factor alpha production by monocytes after endotoxin stimulation

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Diedrich, J. P.; Schäfer, Christian

    1998-01-01

    necrosis factor alpha (TNF-alpha) from Mphi. Further, the efficiency of ethanol to inactivate chemically generated ROS was tested. Significant stimulation of ROS release occurred at endotoxin concentrations of 1 ng/ml or higher in both PMNs and Mphi. Ethanol significantly suppressed the formation of ROS...... identical (6 to 8 ng/ml) in both PMNs and Mphi, independent of the presence of ethanol. In contrast to ROS formation, ethanol had no effect on the amount of TNF-alpha produced by endotoxin-stimulated Mphi. Ethanol was shown to be unable to decrease the levels of chemically generated ROS under physiological......The ability of polymorphonuclear neutrophils (PMNs) and monocytes (Mphi) to produce reactive oxygen species (ROS) has been related closely to their potential in the killing of microorganisms. Ethanol has been shown to impair the generation of ROS in these phagocytes after stimulation with some...

  20. Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

    DEFF Research Database (Denmark)

    Clausen, Bettina H; Lambertsen, Kate L; Babcock, Alicia A

    2008-01-01

    BACKGROUND: Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We...... artery occlusion in mice, validating the results by the use of bone marrow chimeric mice. RESULTS: We found that IL-1beta and TNF-alpha were expressed in largely segregated populations of CD11b+CD45dim microglia and CD11b+CD45high macrophages, with cells expressing both cytokines only rarely. The number...... of Gr1+ granulocytes producing IL-1beta or TNF-alpha was very low, and we observed no IL-1beta- or TNF-alpha-expressing T cells or astrocytes. CONCLUSION: Taken together, the results show that IL-1beta and TNF-alpha are produced by largely segregated populations of microglia and macrophages after...

  1. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system

    DEFF Research Database (Denmark)

    Taupin, V; Renno, T; Bourbonnière, L

    1997-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-alpha in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes...... are a target of immune attack. TNF-alpha also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-alpha at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal...... and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage...

  2. Canadian Association of Gastroenterology Clinical Practice Guidelines: The use of tumour necrosis factor-alpha antagonist therapy in Crohn’s disease

    Science.gov (United States)

    Sadowski, Daniel C; Bernstein, Charles N; Bitton, Alain; Croitoru, Ken; Fedorak, Richard N; Griffiths, Anne

    2009-01-01

    BACKGROUND: Guidelines regarding the use of infliximab in Crohn’s disease were previously published by the Canadian Association of Gastroenterology in 2004. However, recent clinical findings and drug developments warrant a review and update of these guidelines. OBJECTIVE: To review and update Canadian guidelines regarding the use of tumour necrosis factor-alpha antibody therapy in both luminal and fistulizing Crohn’s disease. METHODS: A consensus group of 25 voting participants developed a series of recommendation statements that addressed pertinent clinical questions and gaps in existing knowledge. An iterative voting and feedback process was used in advance of the consensus meeting in conjunction with a systematic literature review to refine the voting statements. These statements were brought to a formal consensus meeting held in Montreal, Quebec (March 2008), wherein each statement underwent discussion, reformulation, voting and subsequent revision until group consensus was obtained (at least 80% agreement). OUTCOME: The 47 voting statements addressed three themes: induction therapy, maintenance therapy and safety issues. As a result of the iterative process, 23 statements achieved consensus and were submitted for publication. CONCLUSION: In the past five years, tumour necrosis factor-alpha antagonist therapy has become a cornerstone in the management of moderate-to-severe Crohn’s disease refractory to conventional treatment algorithms. The evidentiary base supporting the use of these drugs in Crohn’s disease is substantial and strengthened by results from long-term clinical and molecular studies. However, significant gaps in knowledge exist, particularly with regard to treatment failure. Confidence in the safety of these drugs is increasing, provided that therapy is administered in a clinical setting in which potential complications can be readily recognized and treated. PMID:19319383

  3. High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes

    DEFF Research Database (Denmark)

    Sandmand, Marie; Bruunsgaard, Helle; Kemp, Kåre

    2003-01-01

    BACKGROUND: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-alpha are strongly associated with morbidity...... and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown. OBJECTIVE: The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly...... humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age...

  4. Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus.

    Science.gov (United States)

    Garcia, J A; Ferreira, H L; Vieira, F V; Gameiro, R; Andrade, A L; Eugênio, F R; Flores, E F; Cardoso, T C

    2017-06-01

    Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication-induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy. © 2015 John Wiley & Sons Ltd.

  5. Response of tumour necrosis factor alpha (TNF ) in blood and spleen mice that vaccinated with P.berghei radiation

    International Nuclear Information System (INIS)

    Darlina; Tur R; Teja K

    2015-01-01

    Tumor necrosis factor is a glycoprotein derived from helper T lymphocytes that play an important role in the body's response against malaria infection. However, TNF-α has double play that is on appropriate levels will provide protection and healing, while at excessive levels which may be a response to hyperparasitemia. Thus investigated the expression of TNF alpha secreted blood lymphocytes and spleen cells the mice that's infected with 1 x 10 7 P.berghei infectious or inactivated by radiation. Levels of TNF alpha serum and spleen cell culture medium was monitored on days 2, 7, 14 post infection. Monitoring of parasite growth every two days for 60 days. Determination of TNF alpha levels were measure using ELISA. The results showed parasitaemia mice infected with 175 Gy irradiated parasites have pre patent period of 16 days longer than the control (non-irradiated parasites) with low parasitaemia. TNF alpha concentration that secreted spleen cells of mice vaccinated higher than control mice. Concentration of TNF alpha that secreted blood lymphocyte of mice vaccinated lower than control mice. It was concluded that the secretion of TNF alpha by blood lymphocytes caused more pathogenic factors of the parasite, while the secretion of TNF alpha in spleen due to an immune response against the parasite. (author)

  6. alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages.

    Science.gov (United States)

    Taherzadeh, S; Sharma, S; Chhajlani, V; Gantz, I; Rajora, N; Demitri, M T; Kelly, L; Zhao, H; Ichiyama, T; Catania, A; Lipton, J M

    1999-05-01

    The hypothesis that macrophages contain an autocrine circuit based on melanocortin [ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH)] peptides has major implications for neuroimmunomodulation research and inflammation therapy. To test this hypothesis, cells of the THP-1 human monocyte/macrophage line were stimulated with lipopolysaccharide (LPS) in the presence and absence of alpha-MSH. The inflammatory cytokine tumor necrosis factor (TNF)-alpha was inhibited in relation to alpha-MSH concentration. Similar inhibitory effects on TNF-alpha were observed with ACTH peptides that contain the alpha-MSH amino acid sequence and act on melanocortin receptors. Nuclease protection assays indicated that expression of the human melanocortin-1 receptor subtype (hMC-1R) occurs in THP-1 cells; Southern blots of RT-PCR product revealed that additional subtypes, hMC-3R and hMC-5R, also occur. Incubation of resting macrophages with antibody to hMC-1R increased TNF-alpha concentration; the antibody also markedly reduced the inhibitory influence of alpha-MSH on TNF-alpha in macrophages treated with LPS. These results in cells known to produce alpha-MSH at rest and to increase secretion of the peptide when challenged are consistent with an endogenous regulatory circuit based on melanocortin peptides and their receptors. Targeting of this neuroimmunomodulatory circuit in inflammatory diseases in which myelomonocytic cells are prominent should be beneficial.

  7. Tumor necrosis factor alpha and alpha-1 antitrypsin gene variants in Serbian pediatric arterial ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Đorđević Valentina

    2013-01-01

    Full Text Available The etiology of arterial ischemic stroke (AIS in children is complex, and different from that in adults. Although rare, stroke in children is an important cause of mortality and morbidity. There is increasing evidence that genetic factors, including inflammation mediators, have a role in occurrence and outcome of stroke. We have chosen to assess the role of polymorphism -308G/A in the promoter of tumor necrosis factor α (TNFα gene and S and Z mutations in alpha 1-antitrypsin (AAT gene in the etiology of stroke in children. TNFα polymorphism affects plasma levels of this proinflamatory cytokine, and this could contribute to stroke pathology. It has been shown that increased AAT concentration may present a risk for AIS in children. Since S and Z mutations in AAT gene reduce its levels in plasma they could have a protective role in pediatric stroke. In this study twenty six children with AIS and 100 unrelated individuals from Serbian general population were investigated by PCR/RFLP for these gene variations. No statistically significant difference was observed between patients and general population in distribution of genotypes for -308G/A TNFα polymorphism, so its contributory role in the etiology of stroke was not evident in our group of patients. None of the tested AAT gene mutations were found in patients, which is in concordance with the proposed protective role of deficient AAT variants. AIS is a multifactorial disease, with many genes having a modest role in its pathophysiology, so further analyses of their combined effect are needed to elucidate genetic risk factors in the etiology and outcome of stroke in pediatric patients.

  8. Interleukin-8 production in response to tumor necrosis factor-alpha by cholesteatoma keratinocytes in cell culture.

    Science.gov (United States)

    Hilton, Christopher W; Ondrey, Frank G; Wuertz, Beverley R; Levine, Samuel C

    2011-02-01

    Keratinocytes harvested from acquired cholesteatoma and grown in cell culture will demonstrate increased interleukin-8 (IL-8) production in response to tumor necrosis factor (TNF)-alpha as compared with a control keratinocyte cell line. Immunohistochemical studies have identified IL-8 and TNF-alpha, mediators of bony destruction, in tissue samples of cholesteatoma. TNF-alpha stimulates IL-8 production in healthy epidermal keratinocyte cell lines. It is not known whether TNF-alpha stimulates IL-8 production in cultured cholesteatoma keratinocytes. Prospective controlled tissue culture experiment. Tissue from an acquired cholesteatoma was dissociated and grown in keratinocyte serum-free media for 8 weeks. Cholesteatoma keratinocytes and a control cell line of skin epidermal keratinocytes were treated with TNF-alpha. Conditioned media were harvested; production of IL-8 was measured by enzyme-linked immunosorbent assay, and cell counts were performed. At a zero concentration of TNF-alpha, mean production of IL-8 by cholesteatoma keratinocytes was 39,809 pg/mL/24hr/1 × 10(6) cells versus 1,907 pg/mL/24hr/1 × 10(6) cells from skin epidermal keratinocytes, a statistically significant difference (P alpha and a 2.44-fold increase in response to 20 pg/mL of TNF-alpha. The skin epidermal keratinocyte cell line demonstrated a 1.07- and 1.13-fold increase to respective concentrations of TNF-alpha. Cholesteatoma keratinocytes appear to retain cell signaling characteristics in vitro that distinguish them from skin epidermal keratinocytes. This finding may indicate that cholesteatoma keratinocytes undergo a change in behavior in vivo that is preserved after the cells are removed from the inflammatory environment of the middle ear. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  9. Tumour necrosis factor alpha inhibitor therapy and rehabilitation for the treatment of ankylosing spondylitis: a systematic review.

    Science.gov (United States)

    Lubrano, Ennio; Spadaro, Antonio; Amato, Giorgio; Benucci, Maurizio; Cavazzana, Ilaria; Chimenti, Maria Sole; Ciancio, Giovanni; D Alessandro, Giuseppe; Angelis, Rossella De; Lupoli, Salvatore; Lurati, Alfredo Maria; Naclerio, Caterina; Russo, Romualdo; Semeraro, Angelo; Tomietto, Paola; Zuccaro, Carmelo; De Marco, Gabriele

    2015-04-01

    To systematically review the evidence for a synergistic effect of combining rehabilitation with biological anti-tumour necrosis factor (TNF) therapy in patients with ankylosing spondylitis (AS). Data were analysed to identify the most effective rehabilitation programmes, the best endpoints for effectiveness, and patient subgroups most likely to benefit from combination therapy. Systematic MEDLINE and Embase searches were performed to identify studies evaluating rehabilitation programmes and biological therapy in patients with AS. Evidence was categorised by study type, and efficacy, adverse effects and other outcomes were summarised. Of the 75 studies identified, 13 investigated the combination of a rehabilitation programme with TNF inhibitor therapy, while the remainder studied rehabilitation with standard therapy (often not specified). Data from these few studies suggest that combined rehabilitation plus anti-TNF therapy is more effective in terms of symptom severity, disease activity, disability and quality-of-life indices versus biologic alone or rehabilitation with standard medical therapy, or, in non-comparative studies, compared with baseline. The most effective rehabilitation appears to be supervised or in-patient programmes with an educational component. Available data do not provide guidance on most appropriate endpoints or identify patients most likely to benefit from combination therapy. Combined, TNF inhibitor and rehabilitation therapy appear to have a synergistic effect, possibly due to increased adherence to exercise. Exercise regimes are more effective if supervised and include an education component. Further randomized, controlled trials comparing endpoints and investigating longer-term benefits of combining TNF inhibitors with rehabilitation in different AS subgroups are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotalineinduced pulmonary hypertensive rats model

    Directory of Open Access Journals (Sweden)

    Jung Hyun kwon

    2013-03-01

    Full Text Available Purpose: Tumor necrosis factor (TNF-?#6185;s thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-?#6177;ntagonist treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C, single subcutaneous injection of normal saline (0.1 mL/kg; monocrotaline (M, single subcutaneous injection of monocrotaline (60 mg/kg; and monocrotaline + infliximab (M+I, single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg. The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-?#6188;endothelin-1 (ET-1 , endothelin receptor A (ERA , endothelial nitric oxide synthase (eNOS , matrix metalloproteinase (MMP 2, and tissue inhibitor of matrix metalloproteinase (TIMP . Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P&lt;0.05. The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P &lt; 0.05. Expression levels of TNF-?#6944;ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28. Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-?#6944;and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

  11. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Doyle, Mittie K.; Landewé, Robert; Matteson, Eric L.; Wollenhaupt, Jürgen; Gaylis, Norman; Murphy, Frederick T.; Neal, Jeffrey S.; Zhou, Yiying; Visvanathan, Sudha; Hsia, Elizabeth C.; Rahman, Mahboob U.; Ahern, Michael John; Hall, Stephen; Nash, Peter Thomas; Graninger, Winfried; Ebner, Wolfgang; Machold, Klaus; Zamani, Omid; Atkins, Christopher; Beaulieu, André; Bell, Mary; Fitzcharles, Mary Ann; Keystone, Edward; Khraishi, Majed; McKendry, Robert J. R.; Rahman, Proton; Thomason, Glen T. D.; Thorne, J. Carter; Bookman, Arthur; Faraawi, Rafat; Hannonen, Pekka; Leirisalo-Repo, Marjetta; Järvinen, Pentti; Braun, Jürgen; Burmester, Gerd; Fiehn, Christoph; Gruenke, Mathias; Bäuerle, Michael; Hauer, Rolf-Walter; Kellner, Herbert; Rubbert, Andrea; Schewe, Stefan; Sieper, Joachim; Tony, Hans-Peter; Kekow, Jörn; Ching, Daniel Wai Tho; Jones, Peter Brian Barrie; Singh, Gagrath Pradeep

    2009-01-01

    Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid

  12. Tumor necrosis factor-alpha modulates effects of aryl hydrocarbon receptor ligands on cell proliferation and expression of cytochrome P450 enzymes in rat liver "stem-like" cells

    Czech Academy of Sciences Publication Activity Database

    Umannová, Lenka; Zatloukalová, Jiřina; Machala, M.; Krčmář, P.; Májková, Z.; Hennig, B.; Kozubík, Alois; Vondráček, Jan

    2007-01-01

    Roč. 99, č. 1 (2007), s. 79-89 ISSN 0388-1350 R&D Projects: GA ČR(CZ) GA524/05/0595 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : tumor necrosis factor-alpha * xenobiotic metabolizing enzymes * dioxin Subject RIV: BO - Biophysics

  13. Lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells : Intracellular localization of tumor necrosis factor alpha and interleukin 1 beta detected with a three-color immunofluorescence technique

    NARCIS (Netherlands)

    deBont, ESJM; Niemarkt, AE; Tamminga, RYJ; Kimpen, JLL; Kamps, WA; deLeij, LHMF

    1996-01-01

    Lipopolysaccharide (LPS) can induce monocytes to produce various cytokines such as tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta). In the present study, the kinetics of both intracellular and extra cellular accumulation of TNF alpha and IL-1 beta in LPS stimulated

  14. Relationship of tumor necrosis factor alpha genotypes with various biochemical parameters of normal, over weight and obese human subjects

    International Nuclear Information System (INIS)

    Raza, M.; Chaudhary, B.; Shakoori, A.R.

    2008-01-01

    Tumor Necrosis Factor (TNF-alpha) is expressed primarily in adipocytes and elevated levels of this cytokine have been associated with obesity. The purpose of this investigation was to test whether the TNF-alpha -308 polymorphism were associated with insulin resistance or obesity related traits in non-diabetic and diabetic patients visiting Sheikh Zayed Hospital, Lahore, Fatima Hospital and Irfan Clinic in Sargodha. In non diabetic subjects the AA allele carriers, compared with homozygous G allele carriers had significantly lower (28%) triglyceride values and 15% higher HDL yal ues, whereas other parameters tested 81id not show any significant variation. In diabetic patients the AA allele carriers, compared with GG allele carriers, besides having 31 % higher FBS and 26% higher creatinine, had 20% higher cholesterol and 34% higher triglycerides. The HDL values were 14% less, compared to GG allele carriers. In normal subjects (BMI 22.85:1:0.25 kgim2), the AA allele carriers showed 132%, 125%, 65% and 112% higher triglycerides, cholesterol and LDL values compared with GG allele carriers. The HDL and creatinine did not show any significant change. In the overweight subjects (BMI: 27.17+-0.17 kgim/sup 2/) all these values were lower than in AA allele carriers compared with GG allele carriers. The AA allele carries had FBS, triglycerides, cholesterol and LDL 28%, 48%, 14% and 14% lower than in the GG allele' carriers, respectively. In obese subjects, (BMI: 36.73+-0.78kgm/sup 2/), however, the FBS, triglycerides, cholesterol and creatinine values were 5%, 8%, 7% and 14% higher in AA allele carries compared to GG allele carriers, respectively. The LDL content was 8% lower in AA allele carrier as compared with the respective GG allele carriers, It is concluded that replacement of G at -308 with A leads to reduced risk for cardiovascular disease in non-diabetic subject, whereas in diabetic patients this mutation-increases the risk of CVD. Using BMI as index of obesity, it was

  15. Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), interleukin-11 (IL-11) and tumour necrosis factor-alpha (TNF-alpha) in p53-characterised human ovarian carcinomas

    NARCIS (Netherlands)

    Asschert, JGW; Vellenga, E; Hollema, H; van der Zee, AGJ; de Vries, EGE

    1997-01-01

    Ovarian carcinoma is often associated with overexpression of cytokines that may exert autocrine and paracrine growth effects, as well as genetic alterations in (proto)oncogenes and tumour suppressor genes, such as p53. The p53 protein is not only involved in the regulation of cell cycle and

  16. Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Andresen, Lars; Alvarez, Susana

    2006-01-01

    Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development...

  17. Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications.

    Directory of Open Access Journals (Sweden)

    Anne Chastre

    Full Text Available Acute liver failure (ALF due to ischemic or toxic liver injury is a clinical condition that results from massive loss of hepatocytes and may lead to hepatic encephalopathy (HE, a serious neuropsychiatric complication. Although increased expression of tumor necrosis factor-alpha (TNF-α in liver, plasma and brain has been observed, conflicting results exist concerning its roles in drug-induced liver injury and on the progression of HE. The present study aimed to investigate the therapeutic value of etanercept, a TNF-α neutralizing molecule, on the progression of liver injury and HE in mice with ALF resulting from azoxymethane (AOM hepatotoxicity.Mice were administered saline or etanercept (10 mg/kg; i.p. 30 minutes prior to, or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM significantly delayed the onset of coma stages of HE. Etanercept pretreatment attenuated AOM-induced liver injury, as assessed by histological examination, plasma ammonia and transaminase levels, and by hepatic glutathione content. Peripheral inflammation was significantly reduced by etanercept as shown by decreased plasma IL-6 (4.1-fold; p<0.001 and CD40L levels (3.7-fold; p<0.001 compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in brain (1.2-fold; p<0.05, attenuated microglial activation (assessed by OX-42 immunoreactivity, and increased brain glutathione concentrations.These results indicate that systemic sequestration of TNF-α attenuates both peripheral and cerebral inflammation leading to delayed progression of liver disease and HE in mice with ALF due to toxic liver injury. These results suggest that etanercept may provide a novel therapeutic approach for the management of ALF patients awaiting liver transplantation.

  18. The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure

    Directory of Open Access Journals (Sweden)

    Lv Sa

    2009-09-01

    Full Text Available Abstract Background Spontaneous bacterial peritonitis (SBP is a common clinical disease and one of the most severe complications of acute liver failure (ALF. Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1 protein in a mouse model of ALF. Methods We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed. Results Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1 antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. Conclusion TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.

  19. Induction of NKG2D ligands by gamma radiation and tumor necrosis factor-alpha may participate in the tissue damage during acute graft-versus-host disease.

    Science.gov (United States)

    Gannagé, Monique; Buzyn, Agnès; Bogiatzi, Sofia I; Lambert, Marion; Soumelis, Vassili; Dal Cortivo, Liliane; Cavazzana-Calvo, Marina; Brousse, Nicole; Caillat-Zucman, Sophie

    2008-03-27

    Immunopathology of acute graft-versus-host disease (aGVHD) involves secretion of proinflammatory cytokines with subsequent expression of danger signals by injured host tissues. This explanation, however, does not explain the cluster of aGVHD target organs (skin, gut, and liver). NKG2D ligands (MICA/B and ULBP1-3 proteins) are stress-induced molecules that act as danger signals to alert NK and alphabeta or gammadelta CD8 T cells through engagement of the activating NKG2D receptor. We observed a strong and reversible induction of MICA/B expression in skin and liver sections during aGVHD. Tumor necrosis factor-alpha and gamma-radiation up-regulated expression of MICA/B and ULBP proteins in vitro on skin and intestine epithelial cell lines and ex vivo in normal skin explants. This NKG2D-ligand induction was regulated by a complex interplay between NFkB and JNK activation pathways. Our data suggest that NKG2D ligand induction might participate in the amplification loop that leads to tissue damage during aGVHD.

  20. Expression of anti-tumor necrosis factor alpha (TNFα) single-chain variable fragment (scFv) in Spirodela punctata plants transformed with Agrobacterium tumefaciens.

    Science.gov (United States)

    Balaji, Parthasarathy; Satheeshkumar, P K; Venkataraman, Krishnan; Vijayalakshmi, M A

    2016-05-01

    Therapeutic antibodies against tumor necrosis factor alpha (TNFα) have been considered effective for some of the autoimmune diseases such as rheumatoid arthritis, Crohn's diseases, and so on. But associated limitations of the current therapeutics in terms of cost, availability, and immunogenicity have necessitated the need for alternative candidates. Single-chain variable fragment (scFv) can negate the limitations tagged with the anti-TNFα therapeutics to a greater extent. In the present study, Spirodela punctata plants were transformed with anti-TNFα through in planta transformation using Agrobacterium tumefaciens strain, EHA105. Instead of cefotaxime, garlic extract (1 mg/mL) was used to remove the agrobacterial cells after cocultivation. To the best of our knowledge, this report shows for the first time the application of plant extracts in transgenic plant development. 95% of the plants survived screening under hygromycin. ScFv cDNA integration in the plant genomic DNA was confirmed at the molecular level by PCR. The transgenic protein expression was followed up to 10 months. Expression of scFv was confirmed by immunodot blot. Protein expression levels of up to 6.3% of total soluble protein were observed. β-Glucuronidase and green fluorescent protein expressions were also detected in the antibiotic resistant plants. The paper shows the generation of transgenic Spirodela punctuata plants through in planta transformation. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  1. Polymorphism in the tumor necrosis factor-alpha gene (TNFA -308 G/A is not associated with susceptibility to chronic periodontitis in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Paula Cristina Trevilatto

    2016-02-01

    Full Text Available Objective: Tumor necrosis factor-alpha (TNF-α is a major mediator of the immune-inflammatory response and may play an important role in the pathogenesis and progression of chronic periodontitis. Polymorphisms in the promoter of the TNFA gene have been associated with some types of inflammatory diseases. The present study investigated the association between a single-nucleotide polymorphism (SNP of the TNFA (G-308A gene and chronic periodontitis in Brazilians. Methods: One hundred and thirteen (113 over 25 years were divided according to the severity level of periodontal disease: 44 healthy individuals (control group, 31 subjects with moderate and 38 patients with severe periodontitis. Genomic DNA was obtained from epithelial cells. The samples were analyzed for TNFA (G-308A polymorphism using polymerase chain reaction-restriction fragment length polymorphism techniques. The significance of the differences in the genotype frequencies of the polymorphism was assessed by Chi-square test (p<0.05. Results: No significant differences in the genotype distribution and allele frequency were found between control and groups with periodontitis. Conclusion: It was concluded that TNFA (-308 polymorphism was not associated with chronic periodontitis. Other polymorphisms in this or/and other genes of the host inflammatory response might be involved in determining susceptibility to periodontitis in the study population.

  2. Polymorphisms of Tumor Necrosis Factor Alpha in Moroccan Patients with Gastric Pathology: New Single-Nucleotide Polymorphisms in TNF-α−193 (G/A

    Directory of Open Access Journals (Sweden)

    A. Essadik

    2015-01-01

    Full Text Available Polymorphisms in tumor necrosis factor alpha (TNF-α gene are emerging as key determinants of gastric diseases. The TNF-α−308 (G/A and TNF-α−238 (G/A single-nucleotide polymorphisms SNPs are the most extensively studied. However, all these studies are conducted in Caucasian and Asian populations. Thus, for the first time in Africa, we sought to investigate whether polymorphisms in TNF-α gene were associated with the development of gastric pathology in Morocco. Two SNPs located in the promoter region (positions −308 and −238 in TNF-α gene were genotyped in 244 individuals (170 patients and 74 healthy controls. Odds ratios (ORs and 95% confidence intervals (CI were estimated using logistic regression analysis. The TNF-α−238 (G/A genotype was significantly associated with a high risk of gastritis and gastric cancer (GC (P=0.001 and P=0.002, resp.. Furthermore, a new polymorphism located in the promoter region at position −193 in TNF-α gene was identified. The distribution of this SNP was markedly different in patients suffering from ulcers. The association between TNF-α−193 (G/A genotype and high risk of ulcer was significant (P=0.03. These results suggest that the TNF-α−193 (G/A allele has a protective function against gastric cancer by developing ulcer.

  3. The effects of dexamethasone and chlorpromazine on tumour necrosis factor-alpha, interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-10 in human volunteers.

    Science.gov (United States)

    Bleeker, M W; Netea, M G; Kullberg, B J; Van der Ven-Jongekrijg, J; Van der Meer, J W

    1997-01-01

    Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are pro-inflammatory cytokines that play an important role in severe infections, whereas IL-1 receptor antagonist (IL-1ra) and IL-10 are anti-inflammatory cytokines that counteract their effects. Chlorpromazine and dexamethasone protect mice against lethal endotoxaemia by decreasing circulating concentrations of TNF-alpha and IL-1 beta. We investigated whether administration of chlorpromazine or dexamethasone to human volunteers is able to modulate the lipopolysaccharide (LPS)-stimulated cytokine production capacity in whole blood. Blood samples were taken before and several time-points after medication. Circulating cytokine concentrations were low in all samples. LPS-induced TNF-alpha and IL-1 beta production in whole blood was inhibited by dexamethasone treatment, while chlorpromazine had no effect. When peripheral blood mononuclear cells were stimulated in vitro with LPS, the addition of chlorpromazine (1-100 ng/ml) had no modulatory action on TNF-alpha, IL-1 beta, IL-1ra or IL-10 synthesis. The chlorpromazine concentrations measured in circulation of volunteers were eight to 40 times lower than the concentrations shown to be effective in mice. In conclusion, chlorpromazine inhibits TNF-alpha and IL-1 beta production in mice at concentrations that cannot be reached in humans, thus precluding its usage in clinical anti-cytokine strategies. In contrast, dexamethasone is an effective inhibitor of pro-inflammatory cytokine production. PMID:9378493

  4. The change of serum tumor necrosis factor alpha in patients with type 1 diabetes mellitus: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yong-Chao Qiao

    Full Text Available The aim of this study was used meta-analysis to investigate changes of serum tumor necrosis factor-alpha (TNF-α in patients with type 1 diabetes mellitus (T1DM.Relevant literatures were identified from PubMed, Cochrane Library, CNKI, WanFang and Chinese-Cqvip databases (published from January 1, 1999 to September 30, 2016. Eligible reports were included for pooled analysis of serum TNF-α level and subgroup analysis was performed in relation with age, disease duration and ethnicity.A total of 23 articles (1631 T1DM cases, 1429 healthy controls were included for this meta-analysis. Compared with the controls, the patients had significantly increased serum TNF-α level (P < 0.001. Similar results were also found among all subgroup analysis of different age, disease duration and ethnicity (with the exception of Asian (all P < 0.05. Regression analysis indicated that age (P = 0.680, disease duration (P = 0.957, and ethnicity (P = 0.526 of patients were not significant impact factors for the high heterogeneity. The results were stable according to the sensitivity analysis and no publication bias existed in this meta-analysis.Serum TNF-α level in T1DM patients has significantly elevated among all age, disease duration and ethnicity groups.

  5. In vitro infection of bovine monocytes with Mycoplasma bovis delays apoptosis and suppresses production of gamma interferon and tumor necrosis factor alpha but not interleukin-10.

    Science.gov (United States)

    Mulongo, Musa; Prysliak, Tracy; Scruten, Erin; Napper, Scott; Perez-Casal, Jose

    2014-01-01

    Mycoplasma bovis is one of the major causative pathogens of bovine respiratory complex disease (BRD), which is characterized by enzootic pneumonia, mastitis, pleuritis, and polyarthritis. M. bovis enters and colonizes bovine respiratory epithelial cells through inhalation of aerosol from contaminated air. The nature of the interaction between M. bovis and the bovine innate immune system is not well understood. We hypothesized that M. bovis invades blood monocytes and regulates cellular function to support its persistence and systemic dissemination. We used bovine-specific peptide kinome arrays to identify cellular signaling pathways that could be relevant to M. bovis-monocyte interactions in vitro. We validated these pathways using functional, protein, and gene expression assays. Here, we show that infection of bovine blood monocytes with M. bovis delays spontaneous or tumor necrosis factor alpha (TNF-α)/staurosporine-driven apoptosis, activates the NF-κB p65 subunit, and inhibits caspase-9 activity. We also report that M. bovis-infected bovine monocytes do not produce gamma interferon (IFN-γ) and TNF-α, although the level of production of interleukin-10 (IL-10) is elevated. Our findings suggest that M. bovis takes over the cellular machinery of bovine monocytes to prolong bacterial survival and to possibly facilitate subsequent systemic distribution.

  6. Plasma Tumor Necrosis Factor-alpha (TNF-α) Levels Correlate with Disease Severity in Spastic Diplegia, Triplegia, and Quadriplegia in Children with Cerebral Palsy.

    Science.gov (United States)

    Wu, Jianxian; Li, Xueming

    2015-12-11

    BACKGROUND Inflammatory responses in utero and in neonates have been involved in the development of white matter lesions. This study aimed to investigate the role of tumor necrosis factor-alpha (TNF-α) in spastic cerebral palsy. MATERIAL AND METHODS Plasma TNF-α was measured by ELISA in 54 children with spastic cerebral palsy and 28 aged-matched controls. Both groups were split into age subgroups (1-3 vs. 4-12). Gross motor function and activities of daily living were assessed on enrollment and after 6 months of rehabilitation. RESULTS TNF-α was higher in patients with cerebral palsy than in controls in young (P<0.001) and older subjects (P<0.001). TNF-α levels were comparable in both control subgroups (P=0.819). Younger patients with cerebral palsy had significantly higher TNF-α levels compared with older ones (P<0.001). Pre-rehabilitation TNF-α levels correlated with improvements in activities of daily living after rehabilitation (P<0.001). CONCLUSIONS Children with cerebral palsy showed higher plasma levels of TNF-α than controls. In addition, pre-treatment TNF-α levels were correlated with the improvements after rehabilitation therapy.

  7. Decreased Progesterone Receptor B/A Ratio in Endometrial Cells by Tumor Necrosis Factor-Alpha and Peritoneal Fluid from Patients with Endometriosis.

    Science.gov (United States)

    Chae, Uisoo; Min, Jin Young; Kim, Sung Hoon; Ihm, Hyo Jin; Oh, Young Sang; Park, So Yun; Chae, Hee Dong; Kim, Chung Hoon; Kang, Byung Moon

    2016-11-01

    Progesterone resistance is thought to be a major factor that contributes to progression of endometriosis. However, it is not clear what causes progesterone resistance in endometriosis. This study aimed to assess whether cytokines or peritoneal fluid can affect progesterone receptor (PR) expression in endometrial cells and to verify whether PR expression is reduced in endometriosis. The PR-B/A ratio was measured via real-time polymerase chain reaction after in vitro culture, in which endometrial cells were treated with either tumor necrosis factor-alpha (TNF-α), interleukin-1 beta, or peritoneal fluid obtained from women with advanced-stage endometriosis. Immunohistochemistry was performed to compare PR-B expression between eutopic and ectopic endometrial tissues from women with and without advanced-stage endometriosis. The PR-B/A ratio was significantly decreased by treatment with either TNF-α (p=0.011) or peritoneal fluid from women with advanced-stage endometriosis (p=0.027). Immunoreactivity of PR-B expression was significantly lower during the secretory phase than during the proliferative phase in endometrial tissues from control subjects (pendometriosis compared with eutopic endometrium tissues from control subjects. Progesterone resistance in endometriosis may be caused by proinflammatory conditions in the pelvic peritoneal microenvironment.

  8. Tumor Necrosis Factor-Alpha Gene Promoter −308G/A and −238G/A Polymorphisms in Mexican Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Juan Manuel Guzmán-Flores

    2011-01-01

    Full Text Available The association between some Tumor necrosis factor-alpha (TNF-α promoter polymorphisms and Type 2 diabetes mellitus (T2DM remains controversial. Ethnic differences may play a role in these conflicting results. The aim of this study was to investigate the association between −308G/A and −238G/A polymorphisms located in the promoter region of the TNF-α gene and T2DM in Mexican mestizo patients. Nine hundred four individuals (259 patients with T2DM and 645 controls were genotyped for the −308G/A and −238G/A polymorphisms by PCR—RFLP. We found that the −238A allele increased the risk of developing T2DM in Mexican patients (OR = 1.57, 95% CI: 1.07–2.29; p = 0.018. Moreover, we found that the frequency of the GA haplotype (created by the −308G and −238A alleles was significantly increased in patients with T2DM when compared with controls (OR = 1.56, 95% CI: 1.05–2.31; p = 0.026. Our results suggest that the −238G/A polymorphism and a specific haplotype (GA are genetic risk factors for the development of T2DM in Mexican population.

  9. Tumor necrosis factor alpha is a promising circulating biomarker for the development of obstructive sleep apnea syndrome: a meta-analysis.

    Science.gov (United States)

    Li, Qingsheng; Zheng, Xin

    2017-04-18

    Obstructive sleep apnea syndrome (OSAS) is a chronic inflammatory disorder. The relationship between tumor necrosis factor alpha (TNF-alpha) and OSAS has been widely evaluated, but the results thus far remain inconclusive. We thereby decided to quantify the changes of TNF-alpha between OSAS patients and controls by a meta-analysis. This study complies with the MOOSE guidelines. Two reviewers independently searched articles and abstracted relevant data. In total, 47 articles (59 studies) were analyzed, including 2857 OSAS patients and 2115 controls. Overall, OSAS patients had a significantly higher level of circulating TNF-alpha than controls (weighted mean difference [WMD]: 9.66 pg/mL, 95% confidence interval [CI]: 8.66 to 11.24, Pgrades of OSAS. In patients with mild, mild-to-moderate, moderate, moderate-to-severe and severe OSAS, circulating TNF-alpha was higher than respective controls by 0.99, 1.48. 7.79, 10.08 and 8.85 pg/mL, with significant heterogeneity (I2: 91.2%, 74.5%, 97.6%, 99.0% and 98.1%). In conclusion, our findings demonstrated that circulating TNF-alpha was significantly higher in OSAS patients than in controls, and this difference became more pronounced with the more severe grades of OSAS, indicating that TNF-alpha might be a promising circulating biomarker for the development of OSAS.

  10. Lipid profile of rheumatoid arthritis patients treated with anti-tumor necrosis factor-alpha drugs changes according to disease activity and predicts clinical response.

    Science.gov (United States)

    Cacciapaglia, Fabio; Anelli, Maria Grazia; Rinaldi, Angela; Serafino, Lucia; Covelli, Michele; Scioscia, Crescenzio; Iannone, Florenzo; Lapadula, Giovanni

    2014-11-01

    Patients with active rheumatoid arthritis (RA) frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Inflammatory cytokines, and particularly tumor necrosis factor-alpha (TNF-α), are implicated in the pathogenesis of both atherosclerosis and RA, and also involved in the development of the impaired lipid profile detected in active RA. Although anti-TNF-α agents have been proven effective in controlling joint damage and systemic inflammation, controversy remains about the effect of these drugs on the lipid profile; therefore, the aim of our study was to investigate the effect of anti-TNF-α treatment, in combination with disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroid therapy, on the lipid profile of patients with active RA. Our data suggest that the combination anti-TNF-α/DMARDs/steroids do not significantly interfere with the lipid profile of RA patients. However, analysis of clinical response data showed that patients achieving low disease activity or remission seem to have a protective lipid profile, suggesting that better control of inflammation and disease activity can affect lipid metabolism. The available evidence indicates that high inflammation interferes with lipid metabolism, whereas good control of the chronic inflammatory state may positively influence the lipid profile and cardiovascular risk. Low cholesterol levels at baseline could predict a favorable outcome with anti-TNF-α treatment, but these data need to be confirmed by large prospective studies with long-term follow-up. © 2014 Wiley Periodicals, Inc.

  11. Tumor necrosis factor alpha promotes the expression of immunosuppressive proteins and enhances the cell growth in a human bone marrow-derived stem cell culture

    Energy Technology Data Exchange (ETDEWEB)

    Miettinen, Johanna A., E-mail: johanna.miettinen@oulu.fi [Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Pietilae, Mika [Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Salonen, Riikka J. [Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Ohlmeier, Steffen [Proteomics Core Facility, Biocenter Oulu, Department of Biochemistry, University of Oulu, P.O. Box 3000, FIN-90014 Oulu (Finland); Ylitalo, Kari; Huikuri, Heikki V. [Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Lehenkari, Petri [Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland)

    2011-04-01

    Mesenchymal stem cells (MSCs) are widely used in experimental treatments for various conditions that involve normal tissue regeneration via inflammatory repair. It is known that MSCs can secrete multiple soluble factors and suppress inflammation. Even though the effect of MSCs on inflammation has been extensively studied, the effect of inflammation on MSCs is poorly understood. One of the major cytokines released at the site of inflammation is tumor necrosis factor alpha (TNF-{alpha}) which is known to induce MSC invasion and proliferation. Therefore, we wanted to test the effects of TNF-{alpha} exposure on MSCs derived from human bone marrow. We found, as expected, that cell proliferation was significantly enhanced during TNF-{alpha} exposure. However, according to the cell surface marker analysis, the intensity of several antigens in the minimum criteria panel for MSCs proposed by International Society of Cellular Therapy (ISCT) was decreased dramatically, and in certain cases, the criteria for MSCs were not fulfilled. In addition, TNF-{alpha} exposure resulted in a significant but transient increase in human leukocyte antigen and CD54 expression. Additional proteomic analysis by two-dimensional difference gel electrophoresis and mass spectrometry revealed three proteins whose expression levels decreased and 8 proteins whose expression levels increased significantly during TNF-{alpha} exposure. The majority of these proteins could be linked to immunosuppressive and signalling pathways. These results strongly support reactive and immunosuppressive activation of MSCs during TNF-{alpha} exposure, which might influence MSC differentiation stage and capacity.

  12. Azithromycin reduces tumor necrosis factor-alpha production in lipopolysaccharide-stimulated THP-1 monocytic cells by modification of stress response and p38 MAPK pathway.

    Science.gov (United States)

    Ikegaya, S; Inai, K; Iwasaki, H; Naiki, H; Ueda, T

    2009-08-01

    Macrolide antibiotics are known to have a variety of immunomodulatory effects in addition to antimicrobial activity, but the mechanisms of immunomodulation are still unclear. We investigated in vitro the effect of azithromycin on tumor necrosis factor alpha (TNF-alpha) production in lipopolysaccharide (LPS)-stimulated THP-1 cells, a human monocytic cell line, and compared the results with those for other macrolides, minocycline and ofloxacin. In the presence of LPS, treatment with azithromycin (AZM) resulted in a significant decrease in LPS-induced TNF-alpha production compared to that with other antimicrobial agents. the results of phosphorylation of three MAPKs, ERK, JNK and p38, indicated that the phospho-p38 level was reduced by AZM. Ikappab-alpha, an inhibitor of NFkappab, was not disrupted by the antibiotics. LPS-induced TNF-alpha release from THP-1 cells was inhibited in the presence of KNK437, a potent 70-kDa heat shock protein (HSP-70) inhibitor. Interestingly, the induction of HSP-70 by LPS was attenuated with the concurrent addition of AZM in the cells. AZM was found to restrain TNF-alpha production by monocytes at least in part by modifying the HSp-70 and p38 related signaling pathways to LPS stimulation.

  13. Tumor necrosis factor alpha -238 G/A and -308 G/A polymorphisms and soluble TNF-α levels in chronic kidney disease: correlation with clinical variables

    Science.gov (United States)

    Vázquez-Huerta, Diana I; Alvarez-Rodríguez, Bertha A; Topete-Reyes, Jorge F; Muñoz-Valle, José F; Parra-Michel, Renato; Fuentes-Ramírez, Francisco; Salazar-López, María A; Valle, Yeminia; Reyes-Castillo, Zyanya; Cruz-González, A; Brennan-Bourdon, Lorena M; Torres-Carrillo, Norma

    2014-01-01

    Chronic kidney disease (CKD) is characterized by accumulation of proinflammatory cytokines, mainly tumor necrosis factor alpha (TNF-α). Single nucleotide polymorphisms (SNPs) of TNFA gene, including -238 G/A and -308 G/A, have been associated with alteration in the soluble TNF-α (sTNF-α) expression. The aim was to investigate the association of -238 y -308 TNFA gene SNPs with sTNF-α levels in CKD patients. We included 150 CKD patients and 192 control subjects (CS). Both SNPs were genotyped with polymerase chain reaction-restriction fragment length polymorphism technique and sTNF-α levels were measured by enzyme-linked immunosorbent assay. The genotypic distribution of -238 and -308 SNPs was not significantly different between CKD patients and CS (p > 0.001). However, the sTNF-α levels were higher in CKD, compared to CS (p < 0.001). Also, sTNF-α correlated with creatinine (r = 0.279, p = 0.004), urea (r = 0.325, p = 0.001), phosphorus (r = 0.479, p = 0.001), glomerular filtration rate (r = -0.236, p = 0.019) and monocyte count (r = 0.276, p = 0.010). In conclusion, elevated sTNF-α levels are associated with CKD. However, the -238 and -308 TNFA gene SNPs were not associated with susceptibility to CKD and sTNF-α levels in a Mexican population. PMID:25232395

  14. Comparison of interferon {gamma} release assays and conventional screening tests before tumour necrosis factor {alpha} blockade in patients with inflammatory arthritis.

    LENUS (Irish Health Repository)

    Martin, J

    2012-02-01

    OBJECTIVE: To compare the performance of two interferon gamma release assays (IGRAs) and conventional screening tests in patients with inflammatory arthritis undergoing screening for latent tuberculosis infection (LTBI) before treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds. METHODS: Successive patients were subjected to conventional LTBI screening, including a tuberculin skin test (TST). The T-SPOT.TB test was performed on all patients and the QuantiFERON-TB Gold test was performed on a large subset. The results of the IGRAs were compared with the results of conventional screening tests. RESULTS: A total 150 patients were evaluated. The majority (57.9%) had rheumatoid arthritis. Previous vaccination with Bacille Calmette-Guerin was confirmed in 82% of patients. No patient had received prior anti-TB treatment. A total of 57 patients (38.0%) had at least one positive conventional risk factor. In contrast, an unequivocally positive T-SPOT.TB test was seen in only 14\\/143 (9.8%). There was 98.2% agreement between the two IGRAs. Statistically significant associations were found between each of the IGRAs and both TST and risk history, but not chest x-ray (CXR). A positive IGRA result was significantly associated with increased age. TB was not reactivated in any patient during the follow-up period. Interpretation: This study suggests that IGRAs may be useful when screening for LTBI before anti-TNFalpha therapy in patients with immune-mediated inflammatory diseases. The observations reported here also highlight the inadequate performance of CXR as a marker of LTBI.

  15. Effects of aqueous extracts of Taraxacum Officinale on expression of tumor necrosis factor-alpha and intracellular adhesion molecule 1 in LPS-stimulated RMMVECs.

    Science.gov (United States)

    Hu, Ge; Wang, Junjie; Hong, Dong; Zhang, Tao; Duan, Huiqin; Mu, Xiang; Yang, Zuojun

    2017-01-11

    Mastitis gives rise to big financial burden to farm industry (mainly dairy production) and public health. Its incidence is currently high and therefore, highly effective treatments for therapy, especially with natural products are required. Taraxacum officinale has been reported to use for anti-inflammation. However, its effect on endothelium during mastitis has not been reported. We firstly established inflammation experimental model of rat mammary microvascular endothelial cells (RMMVECs). We evaluated the effects of dandelion leaf aqueous extracts (DAE) on LPS-induced production of inflammatory mediators in RMMVECs by enzyme-linked immunosorbent assay and Western blot. We treated RMMVECs with 1 μg/ml LPS for 4 h and then incubated with 10, 100 and 200 μg/mL DAE for 4, 8, 12 and 24 h. The expression (mRNA and protein level) of targets (tumor necrosis factor-alpha (TNF- α) and Intracellular Adhesion Molecule 1 (ICAM1) was analyzed by employing real-time PCR and Western blots. The in vivo anti-inflammatory effect of DAE on mastitis within an Staphylococcus aureus-induced mouse model was also determined. The obtained results showed that dandelion extracts at the concentration of 100 and 200 μg/mL could significantly inhibit both TNF-α and ICAM-1 expression in all time points checked while 10 μg/mL of dandelion only suppress both expression at 8 and 12 h post-treatment. The in vivo tests showed that the DAE inhibited the expression of TNF-α and ICAM-1 in a time-dependent manner. All results suggest that the endothelium may use as as a possible target of dandelion for anti-inflammation.

  16. Effect of deficiency of tumor necrosis factor alpha or both of its receptors on Streptococcus pneumoniae central nervous system infection and peritonitis.

    Science.gov (United States)

    Wellmer, A; Gerber, J; Ragheb, J; Zysk, G; Kunst, T; Smirnov, A; Brück, W; Nau, R

    2001-11-01

    Tumor necrosis factor alpha (TNF-alpha) and TNF-beta are key mediators in bacterial inflammation. We therefore examined the role of TNF-alpha and its two receptors in murine pneumococcal central nervous system infection. TNF-alpha knockout mice and age- and sex-matched controls and TNF receptor (p55 and p75)-deficient mice and heterozygous littermates were infected intracerebrally with a Streptococcus pneumoniae type 3 strain. Mice were monitored until death or were killed 36 h after infection. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration and neuronal damage were assessed by histological scores. TNF-alpha-deficient mice died earlier than the controls after intracerebral infection although overall survival was similar. TNF-alpha deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in brain homogenates. However, it caused a substantial rise of the concentration of S. pneumoniae cells in blood and spleen. Spleen bacterial titers were also increased in p55- and p75-deficient mice. TNF receptor-deficient mice showed decreased meningeal inflammation. Neuronal damage was not affected by either TNF-alpha or TNF receptor deficiency. In a murine model of pneumococcal peritonitis, 10(2) CFU of S. pneumoniae produced fatal peritonitis in TNF-alpha-deficient, but not wild-type, mice. Early leukocyte influx into the peritoneum was impaired in TNF-alpha-deficient mice. The lack of TNF-alpha or its receptors renders mice more susceptible to S. pneumoniae infections.

  17. Tumor necrosis factor alpha inhibits the suppressive effect of regulatory T cells on the hepatitis B virus-specific immune response.

    Science.gov (United States)

    Stoop, Jeroen N; Woltman, Andrea M; Biesta, Paula J; Kusters, Johannes G; Kuipers, Ernst J; Janssen, Harry L A; van der Molen, Renate G

    2007-09-01

    Chronicity of hepatitis B virus (HBV) infection is characterized by a weak immune response to the virus. CD4+CD25+ regulatory T cells (Treg) are present in increased numbers in the peripheral blood of chronic HBV patients, and these Treg are capable of suppressing the HBV-specific immune response. The aim of this study was to abrogate Treg-mediated suppression of the HBV-specific immune response. Therefore, Treg and a Treg-depleted cell fraction were isolated from peripheral blood of chronic HBV patients. Subsequently, the suppressive effect of Treg on the response to HBV core antigen (HBcAg) and tetanus toxin was compared, and the effect of exogenous tumor necrosis factor alpha (TNF-alpha), interleukin-1-beta (IL-1beta), or neutralizing antibodies against interleukin-10 (IL-10) or transforming growth factor beta (TGF-beta) on Treg-mediated suppression was determined. The results show that Treg of chronic HBV patients had a more potent suppressive effect on the response to HBcAg compared with the response to tetanus toxin. Neutralization of IL-10 and TGF-beta or exogenous IL-1beta had no effect on Treg-mediated suppression of the anti-HBcAg response, whereas exogenous TNF-alpha partially abrogated Treg-mediated suppression. Preincubation of Treg with TNF-alpha demonstrated that TNF-alpha had a direct effect on the Treg. No difference was observed in the type II TNF receptor expression by Treg from chronic HBV patients and healthy controls. Treg-mediated suppression of the anti-HBV response can be reduced by exogenous TNF-alpha. Because chronic HBV patients are known to produce less TNF-alpha, these data implicate an important role for TNF-alpha in the impaired antiviral response in chronic HBV.

  18. Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy

    Directory of Open Access Journals (Sweden)

    Beatriz Fernández-Vega

    2016-03-01

    Full Text Available Aims: To report a case of wet age-related macular degeneration (wet-AMD refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α drug, for concomitant Crohn's disease. Methods: Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment. Best-corrected visual acuity (BCVA was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT. Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results: A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg for a period of 40 months with intervals of 1-6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks. During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions: We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes.

  19. Induction of Programmed Cell Death by Parvovirus H-1 in U937 Cells: Connection with the Tumor Necrosis Factor Alpha Signalling Pathway

    Science.gov (United States)

    Rayet, Béatrice; Lopez-Guerrero, José-Antonio; Rommelaere, Jean; Dinsart, Christiane

    1998-01-01

    The human promonocytic cell line U937 undergoes apoptosis upon treatment with tumor necrosis factor alpha (TNF-α). This cell line has previously been shown to be very sensitive to the lytic effect of the autonomous parvovirus H-1. Parvovirus infection leads to the activation of the CPP32 ICE-like cysteine protease which cleaves the enzyme poly(ADP-ribose)polymerase and induces morphologic changes that are characteristic of apoptosis in a way that is similar to TNF-α treatment. This effect is also observed when the U937 cells are infected with a recombinant H-1 virus which expresses the nonstructural (NS) proteins but in which the capsid genes are replaced by a reporter gene, indicating that the induction of apoptosis can be assigned to the cytotoxic nonstructural proteins in this cell system. The c-Myc protein, which is overexpressed in U937 cells, is rapidly downregulated during infection, in keeping with a possible role of this product in mediating the apoptotic cell death induced by H-1 virus infection. Interestingly, four clones (designated RU) derived from the U937 cell line and selected for their resistance to H-1 virus (J. A. Lopez-Guerrero et al., Blood 89:1642–1653, 1997) failed to decrease c-Myc expression upon treatment with differentiation agents and also resisted the induction of cell death after TNF-α treatment. Our data suggest that the RU clones have developed defense strategies against apoptosis, either by their failure to downregulate c-Myc and/or by activating antiapoptotic factors. PMID:9765434

  20. Neuronal injury and tumor necrosis factor-alpha immunoreactivity in the rat hippocampus in the early period of asphyxia-induced cardiac arrest under normothermia

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    Hyun-Jin Tae

    2017-01-01

    Full Text Available Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest (CA. In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature at 37 ± 0.5°C, and then observed the survival rate during the post-resuscitation phase. We examined neuronal damage in the hippocampus using cresyl violet (CV and Fluore-Jade B (F-J B staining, and pro-inflammatory response using ionized calcium-binding adapter molecule 1 (Iba-1, glial fibrillary acidic protein (GFAP, and tumor necrosis factor-alpha (TNF-α immunohistochemistry in the hippocampus after asphyxial CA in rats under normothermia. Our results show that the survival rate decreased gradually post-CA (about 63% at 6 hours, 37% at 1 day, and 8% at 2 days post-CA. Rats were sacrificed at these points in time post-CA, and no neuronal damage was found in the hippocampus until 1 day post-CA. However, some neurons in the stratum pyramidale of the CA region in the hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1 region did not change until 1 day post-CA, and they were activated (enlarged cell bodies with short and thicken processes in all layers 2 days post-CA. Meanwhile, GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA. TNF-α immunoreactivity decreased significantly in neurons of the stratum pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day post-CA, and increased significantly again 2 days post-CA. These findings suggest that low survival rate of normothermic rats in the early period of asphyxia-induced CA is related to increased TNF-α immunoreactivity, but not to neuronal damage in the hippocampal CA1 region.

  1. Experimental study on inhibitory effect of niacinamide on tumor necrosis factor-alpha-induced matrix degradation of annulus fibrous tissue in vitro.

    Science.gov (United States)

    Xu, Runbing; Shao, Zengwu; Xiong, Liming

    2008-10-01

    The inhibitory effect of niacinamide on tumor necrosis factor-alpha (TNF-alpha) induced annulus fibrous (AF) degradation was assessed, and the mechanism of the inhibition was investigated. Chiba's intervertebral disc (IVD) culture model was established. Forty-eight IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups (12 IVDs in each group), and various concentrations of niacinamide and TNF-alpha were added to the medium for intervention: negative control group, niacinamide control group (0.5 mg/mL niacinamide), degeneration group (10 ng/mL TNF-alpha), and treatment group (0.5 mg/mL niacinamide and 10 ng/mL TNF-alpha). After one week's culture, AFs were collected for glycosaminoglycan (GS) content measurement, safranin O-fast green staining, and immunohistochemical staining for type I, II collagen and cysteine containing aspartate specific protease-3 (Caspase-3). It was found that the GS content in treatment group was increased by about 48% as compared with degeneration group (t=16.93, Pniacinamide control group (t=0.71, P=0.667). Safranine O-fast green staining exhibited higher staining density and better histological structure of AF in the treatment group as compared with the degeneration group. Immunohistochemical staining for both Type I and II collagen demonstrated that lamellar structure and continuity of collagen in treatment group were better reserved than in degeneration group. Positive staining rate of Caspase-3 in AFs of negative control group, niacinamide control group, degeneration group and treatment group was 3.4%, 4.3%, 17.9% and 10.3% respectively. The positive rate in treatment group was significantly lower than in degeneration group (Pniacinamide could effectively alleviate TNF-alpha induced destruction and synthesis inhibition of matrix ingredients in AFs. The inhibition may be related with reduction of expression of Caspase-3. Thus, niacinamide is of potential for IVD degeneration clinical treatment.

  2. Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.

    Science.gov (United States)

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-15

    A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Engineering N-terminal domain of tissue inhibitor of metalloproteinase (TIMP)-3 to be a better inhibitor against tumour necrosis factor-alpha-converting enzyme.

    Science.gov (United States)

    Lee, Meng-Huee; Verma, Vandana; Maskos, Klaus; Nath, Deepa; Knäuper, Vera; Dodds, Philippa; Amour, Augustin; Murphy, Gillian

    2002-01-01

    We previously reported that full-length tissue inhibitor of metalloproteinase-3 (TIMP-3) and its N-terminal domain form (N-TIMP-3) displayed equal binding affinity for tissue necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE). Based on the computer graphic of TACE docked with a TIMP-3 model, we created a number of N-TIMP-3 mutants that showed significant improvement in TACE inhibition. Our strategy was to select those N-TIMP-3 residues that were believed to be in actual contact with the active-site pockets of TACE and mutate them to amino acids of a better-fitting nature. The activities of these mutants were examined by measuring their binding affinities (K(app)(i)) and association rates (k(on)) against TACE. Nearly all mutants at position Thr-2 exhibited slightly impaired affinity as well as association rate constants. On the other hand, some Ser-4 mutants displayed a remarkable increase in their binding tightness with TACE. In fact, the binding affinities of several mutants were less than 60 pM, beyond the sensitivity limits of fluorimetric assays. Further studies on cell-based processing of pro-TNF-alpha demonstrated that wild-type N-TIMP-3 and one of its tight-binding mutants, Ser-4Met, were capable of inhibiting the proteolytic shedding of TNF-alpha. Furthermore, the Ser-4Met mutant was also significantly more active (P<0.05) than the wild-type N-TIMP-3 in its cellular inhibition. Comparison of N-TIMP-3 and full-length TIMP-3 revealed that, despite their identical TACE-interaction kinetics, the latter was nearly 10 times more efficient in the inhibition of TNF-alpha shedding, with concomitant implications for the importance of the TIMP-3 C-terminal domain in vivo. PMID:11988096

  4. Tumor necrosis factor alpha protects against lethal West Nile virus infection by promoting trafficking of mononuclear leukocytes into the central nervous system.

    Science.gov (United States)

    Shrestha, Bimmi; Zhang, Bo; Purtha, Whitney E; Klein, Robyn S; Diamond, Michael S

    2008-09-01

    West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans, especially in immunocompromised individuals. Previous studies have shown essential protective roles for antiviral cytokines (e.g., alpha interferon [IFN-alpha] and IFN-gamma) against WNV in mice. However, studies using cell culture offer conflicting answers regarding whether tumor necrosis factor alpha (TNF-alpha) has an anti-WNV function. To test the biological significance of TNF-alpha against WNV in vivo, experiments were performed with TNF receptor-1 (TNF-R1)-deficient and TNF-alpha-depleted C57BL/6 mice. TNF-R1(-/-) mice had enhanced mortality and decreased survival time after WNV infection compared to congenic wild-type mice. Consistent with this, administration of a neutralizing anti-TNF-alpha monoclonal antibody also decreased survival after WNV infection. Relatively small differences in viral burdens in peripheral tissues of TNF-R1(-/-) mice were observed, and this occurrence correlated with a modest antiviral effect of TNF-alpha on primary macrophages but not dendritic cells. In contrast, the viral titers detected in the central nervous systems of TNF-R1(-/-) mice were significantly increased compared to those of wild-type mice, although TNF-alpha did not have a direct antiviral effect in primary neuron cultures. Whereas no defect in priming of adaptive B- and T-cell responses in TNF-R1(-/-) mice was observed, there were significant reductions in accumulations of CD8+ T cells and macrophages in the brain. Our data are most consistent with a model in which interaction of TNF-alpha with TNF-R1 protects against WNV infection by regulating migration of protective inflammatory cells into the brain during acute infection.

  5. Tumour necrosis factor-alpha antagonists in the management of rheumatoid arthritis in the elderly: a review of their efficacy and safety.

    Science.gov (United States)

    Radovits, Beáta J; Kievit, Wietske; Laan, Roland F J M

    2009-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that frequently affects people aged >or=65 years, causing significant impairment with pain and functional disability. Elderly RA patients have specific problems, including co-morbid diseases, numerous concomitant medications, greater number of damaged joints as a result of longer disease duration and often a more severe disease presentation in elderly-onset RA. These factors, together with an age-related decline in the immune defence mechanisms, make elderly patients more vulnerable. The new era of biologic medications has made intensive treatment of RA patients possible. Anti-tumour necrosis factor-alpha (anti-TNFalpha) agents can cause a dramatic improvement in disease activity and functional capacity, making complete remission of RA a possible target. TNFalpha has been shown to play an important role in both the healthy aging process and age-related diseases such as RA. Targeting this cytokine in elderly patients is therefore reasonable. However, it is not clear whether treatment effects can be reached to the same extent in both elderly and younger patients and whether anti-TNFalpha treatment specifically increases the risk of certain adverse events in elderly RA patients. This review discusses the currently available evidence relating to the efficacy and safety of anti-TNFalpha medication in RA patients aged >or=65 years treated in clinical trials and observational studies. Despite a slightly less robust effect in elderly patients, anti-TNFalpha treatment has a similar long-term efficacy in patients aged >or=65 years and patients aged relatively safe in the treatment of elderly RA patients, treatment with corticosteroids significantly elevated the risk of serious infections. Corticosteroids are frequently used in elderly patients, but the evidence suggests that preference should increasingly be given to anti-TNFalpha agents, for which the expected benefits will mostly outweigh the modestly increased

  6. Differential Gamma Interferon- and Tumor Necrosis Factor Alpha-Driven Cytokine Response Distinguishes Acute Infection of a Metatherian Host with Toxoplasma gondii and Neospora caninum

    Science.gov (United States)

    Donahoe, Shannon L.; Phalen, David N.; McAllan, Bronwyn M.; O'Meally, Denis; McAllister, Milton M.; Ellis, John

    2017-01-01

    ABSTRACT Toxoplasma gondii and Neospora caninum (both Apicomplexa) are closely related cyst-forming coccidian parasites that differ significantly in their host ranges and ability to cause disease. Unlike eutherian mammals, Australian marsupials (metatherian mammals) have long been thought to be highly susceptible to toxoplasmosis and neosporosis because of their historical isolation from the parasites. In this study, the carnivorous fat-tailed dunnart (Sminthopsis crassicaudata) was used as a disease model to investigate the immune response and susceptibility to infection of an Australian marsupial to T. gondii and N. caninum. The disease outcome was more severe in N. caninum-infected dunnarts than in T. gondii-infected dunnarts, as shown by the severity of clinical and histopathological features of disease and higher tissue parasite burdens in the tissues evaluated. Transcriptome sequencing (RNA-seq) of spleens from infected dunnarts and mitogen-stimulated dunnart splenocytes was used to define the cytokine repertoires. Changes in mRNA expression during the time course of infection were measured using quantitative reverse transcription-PCR (qRT-PCR) for key Th1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), Th2 (interleukin 4 [IL-4] and IL-6), and Th17 (IL-17A) cytokines. The results show qualitative differences in cytokine responses by the fat-tailed dunnart to infection with N. caninum and T. gondii. Dunnarts infected with T. gondii were capable of mounting a more effective Th1 immune response than those infected with N. caninum, indicating the role of the immune response in the outcome scenarios of parasite infection in this marsupial mammal. PMID:28348050

  7. A comprehensive study of tumor necrosis factor-alpha genetic polymorphisms, its expression in skin and relation to histopathological features in psoriasis

    Directory of Open Access Journals (Sweden)

    Nikhil N Moorchung

    2015-01-01

    Full Text Available Background: Tumor necrosis factor-alpha (TNFα is an important inflammatory mediator in psoriasis and several genetic polymorphisms of this cytokine have been reported. Majority of studies have focused on the increased G- A polymorphism at the -308 position in psoriasis. There has been no comprehensive study evaluating the genetic polymorphisms, TNFα expression in the skin and histopathology. We are undertaking this study to outline TNFα genetic polymorphisms, its skin expression and histopathological correlation to help determine its role at the genetic and protein level. Materials and Methods : 112 patients of psoriasis and 243 healthy controls were included in this prospective study. 5 ml of peripheral blood was collected to study the TNFα genetic polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Histopathological analysis of biopsies from the 112 patients were done using visual analogue scale and correlated with the findings. 61 of these cases were analyzed for TNFα expression by immunohistochemistry. The results of study were statistically analyzed using SPSS 13.0 statistical package program. Results: A strong association of TNFα -308 G/A polymorphism in psoriasis cases was detected. The A allele of the TNFα -308 G/A polymorphism occurs rarely in the Indian population, however there is an over representation of this allele in psoriatic patients. There was no association seen between TNFα genotype and histopathological severity of psoriasis. Conclusion: The study emphasized the central role of TNFα in the pathogenesis of psoriasis. TNFα genotyping may be helpful in identifying subjects in whom anti-TNFα therapeutic strategies may be tried.

  8. HBV Reactivation in Patients Treated with Antitumor Necrosis Factor-Alpha (TNF-α Agents for Rheumatic and Dermatologic Conditions: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Fabrizio Cantini

    2014-01-01

    Full Text Available Introduction. Antitumor necrosis factor-alpha (TNF-α agents are widely used for treatment of rheumatic and dermatological diseases. We conducted the systematic review and meta-analysis to assess the prevalence of HBV reactivation among patients treated with anti-TNF-α. Methods and Findings. A comprehensive literature search of MEDLINE, Scopus, and ISI Web of Knowledge databases was conducted. From 21 studies included in the systematic review, 9 included patients with occult chronic HBV infection and 6 included patients with overt infection while 6 addressed both groups. Based on 10 studies eligible for meta-analysis we report pooled estimate of HBV reactivation of 4.2% (95% CI: 1.4–8.2%, I2: 74.7%. The pooled prevalence of reactivation was 3.0% (95% CI: 0.6–7.2, I2: 77.1% for patients with occult infection, and 15.4% (95% CI: 1.2–41.2%, I2: 79.9% for overt infection. The prevalence of reactivation was 3.9% (95% CI: 1.1–8.4%, I2: 51.1% for treatment with etanercept and 4.6% (95% CI: 0.5–12.5%, I2: 28.7% for adalimumab. For subgroup of patients without any antiviral prophylaxis the pooled reactivation was 4.0% (95% CI: 1.2–8.3%, I2: 75.6%. Conclusion. Although HBV reactivation rate is relatively low in patients treated with anti-TNF-α for rheumatic and dermatological conditions, the antiviral prophylaxis would be recommended in patients with overt chronic HBV infection.

  9. Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line.

    Science.gov (United States)

    Baker, Olga J; Camden, Jean M; Redman, Robert S; Jones, Jonathan E; Seye, Cheikh I; Erb, Laurie; Weisman, Gary A

    2008-11-01

    Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-alpha and IFN-gamma decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current (I(sc)) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y(2) nucleotide receptor agonist. In contrast, TNF-alpha and IFN-gamma had no effect on agonist-induced increases in the intracellular calcium concentration [Ca(2+)](i) in Par-C10 cells. Furthermore, treatment of Par-C10 cell monolayers with TNF-alpha and IFN-gamma increased paracellular permeability to normally impermeant proteins, altered cell and TJ morphology, and downregulated the expression of the TJ protein, claudin-1, but not other TJ proteins expressed in Par-C10 cells. The decreases in TER, agonist-induced transepithelial anion secretion, and claudin-1 expression caused by TNF-alpha, but not IFN-gamma, were reversible by incubation of Par-C10 cell monolayers with cytokine-free medium for 24 h, indicating that IFN-gamma causes irreversible inhibition of cellular activities associated with fluid secretion in salivary glands. Our results suggest that cytokine production is an important contributor to secretory dysfunction in SS by disrupting TJ integrity of salivary epithelium.

  10. B-lymfocytdepletring og andre biologiske behandlingsmuligheder ved Graves' oftalmopatiTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    El, Fassi D.; Hegedus, L.; Nielsen, Claus Henrik

    2008-01-01

    The current medical treatment options for Graves' ophthalmopathy (GO) are unsatisfactory. Recent treatment of GO patients with the B-lymphocyte depleting monoclonal antibody rituximab or with the anti-tumor necrosis factor-alpha agents etanercept and infliximab has shown promising results. We...... discuss the use of these and other biological agents targeting B lymphocytes, T-lymphocyte interaction with antigen-presenting cells, or cytokines in the future treatment of GO Udgivelsesdato: 2008/6/9...

  11. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2

    OpenAIRE

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan

    2017-01-01

    Tumor necrosis factor alpha (TNF?) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNF? on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNF? stimulus. We observed that HepG2 cell revealed a higher resistance to TNF?-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By usin...

  12. Spironolactone inhibits production of proinflammatory cytokines, including tumour necrosis factor-alpha and interferon-gamma, and has potential in the treatment of arthritis

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, P R; Rieneck, K

    2003-01-01

    and interleukin 6 (70-90% inhibition). Release of these cytokines was also suppressed when testing whole blood from RA patients receiving 50 mg spironolactone twice daily, indicating that pharmaceutical use of the drug may suppress the release of inflammatory cytokines. Spironolactone therapy was generally well...

  13. Association of apoptosis with the inhibition of extracellular signal-regulated protein kinase activity in the tumor necrosis factor alpha-resistant ovarian carcinoma cell line UCI 101.

    Science.gov (United States)

    Yazlovitskaya, E M; Pelling, J C; Persons, D L

    1999-05-01

    Tumor necrosis factor-alpha (TNF alpha) can function as both an autocrine and a paracrine growth factor and may therefore play a role in ovarian tumor progression. TNF alpha initiates multiple cellular responses, many of which are mediated through the mitogen-activated protein kinase pathways, which transduce signals from the TNF alpha receptors through the cytoplasm to the nucleus, resulting in regulation of gene expression. We examined the role of c-jun N-terminal kinase 1 (JNK1) and extracellular signal-regulated protein kinase (ERK) 1 and 2 in the cellular growth response to TNF alpha in the ovarian carcinoma cell line UCI 101. JNK1 activity was increased to a maximum level ninefold above the basal level after 10-20 min of treatment with 10 ng/mL TNF alpha. A maximum threefold induction of ERK1/2 activity was observed after 1 min of treatment. At concentrations up to 100 ng/mL, TNF alpha had neither a stimulatory nor an inhibitory effect on growth of UCI 101 cells. However, inhibition of TNF alpha-induced ERK1/2 activity by the MAP/ERK kinase 1 inhibitor PD 98059 resulted in 60% inhibition of cell growth in TNF alpha-treated UCI 101 cells. This decrease in cell growth was accompanied by apoptosis, as demonstrated by the presence of a 180-bp DNA ladder. Thus, the inhibition of TNF alpha-induced ERK1/2 activity was associated with induction of apoptosis in the TNF alpha-resistant cell line UCI 101. Inhibition of TNF alpha-induced ERK1/2 activity was accompanied by a subsequent transient increase in TNF alpha-induced JNK1 activity. The significance of this increase with respect to apoptosis induction remains to be determined. These findings demonstrated that ERK1/2 activity can modulate cellular sensitivity to TNF alpha and suggested that the balance between the levels of ERK1/2 and JNK1 activation may be critical in the cellular growth response to TNF alpha.

  14. HIV-1 transgene expression in rats induces differential expression of tumor necrosis factor alpha and zinc transporters in the liver and the lung

    Directory of Open Access Journals (Sweden)

    Guidot David M

    2011-10-01

    Full Text Available Abstract Background Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1-related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are useful for studying the systemic effects of these proteins independently of viral infection. We have previously shown that HIV-1 transgene expression (and therefore, HIV-1-related protein expression in rats decreases alveolar macrophage zinc levels and phagocytic capacity by unknown mechanisms. We hypothesized that HIV-1 transgene expression induces chronic inflammation and zinc sequestration within the liver and thereby decreases zinc bioavailability in the lung. We examined the expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα, the zinc storage protein, metallothionein (MT1, and the zinc exporter, ZNT1 in the livers and the lungs of wild type and HIV-1 transgenic rats ± dietary zinc supplementation. In addition, we measured zinc levels, the zinc importing protein ZIP1, and the phagocytic capacity in the alveolar macrophages. Results HIV-1 transgene expression increased the liver-specific expression of TNFα, suggesting a chronic inflammatory response within the liver in response to HIV-1-related protein expression. In parallel, HIV-1 transgene expression significantly increased MT1 and ZNT1 expression in the liver as compared to the lung, a pattern that is consistent with zinc sequestration in the liver as occurs during systemic inflammation. Further, HIV-1 transgene expression decreased intracellular zinc levels and increased expression of ZIP1 in the alveolar macrophages, a pattern consistent with zinc deficiency, and decreased their bacterial phagocytic capacity. Interestingly, dietary zinc supplementation in HIV-1 transgenic rats decreased gene expression of TNFα, MT1, and ZNT1 in the liver while simultaneously increasing their expression in the lung. In parallel

  15. Nuclear factor-kappa B family member RelB inhibits human immunodeficiency virus-1 Tat-induced tumor necrosis factor-alpha production.

    Directory of Open Access Journals (Sweden)

    Michelle Kiebala

    2010-07-01

    Full Text Available Human Immunodeficiency Virus-1 (HIV-1-associated neurocognitive disorder (HAND is likely neuroinflammatory in origin, believed to be triggered by inflammatory and oxidative stress responses to cytokines and HIV protein gene products such as the HIV transactivator of transcription (Tat. Here we demonstrate increased messenger RNA for nuclear factor-kappa B (NF-kappaB family member, transcription factor RelB, in the brain of doxycycline-induced Tat transgenic mice, and increased RelB synthesis in Tat-exposed microglial cells. Since genetic ablation of RelB in mice leads to multi-organ inflammation, we hypothesized that Tat-induced, newly synthesized RelB inhibits cytokine production by microglial cells, possibly through the formation of transcriptionally inactive RelB/RelA complexes. Indeed, tumor necrosis factor-alpha (TNFalpha production in monocytes isolated from RelB deficient mice was significantly higher than in monocytes isolated from RelB expressing controls. Moreover, RelB overexpression in microglial cells inhibited Tat-induced TNFalpha synthesis in a manner that involved transcriptional repression of the TNFalpha promoter, and increased phosphorylation of RelA at serine 276, a prerequisite for increased RelB/RelA protein interactions. The Rel-homology-domain within RelB was necessary for this interaction. Overexpression of RelA itself, in turn, significantly increased TNFalpha promoter activity, an effect that was completely blocked by RelB overexpression. We conclude that RelB regulates TNFalpha cytokine synthesis by competitive interference binding with RelA, which leads to downregulation of TNFalpha production. Moreover, because Tat activates both RelB and TNFalpha in microglia, and because Tat induces inflammatory TNFalpha synthesis via NF-kappaB, we posit that RelB serves as a cryoprotective, anti-inflammatory, counter-regulatory mechanism for pathogenic NF-kappaB activation. These findings identify a novel regulatory pathway for

  16. The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in South African women with cervical cancer and control women

    Directory of Open Access Journals (Sweden)

    Williamson Anna-Lise

    2006-01-01

    Full Text Available Abstract Background Cervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV. Although the incidence of genital HPV infection in various population groups is high, most of these regress without intervention. Investigating genetic host factors and cellular immune responses, particularly cytokines, could help to understand the association between genital HPV infection and carcinogenesis. The tumor necrosis factor alpha (TNF-α cytokine plays an important role in all stages of cervical cancer and has the ability to induce the regression of human tumors. Therefore the aim of the study was to investigate the allelic distribution of -308 TNF-α gene polymorphism in South African women with cervical cancer compared to control women. Methods Included in our study were women with histologically proven cancer of the cervix (n = 244 and hospital-based controls (n = 228. All patients and controls were from mixed race and black population groups in South Africa. The detection of a bi-allelic -308 (A/G polymorphism in the promoter region of TNF-α was investigated using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR technique. The distributions of the allelic frequencies were stratified in both patients and controls into two South African ethnic population groups. Results In this study we observed no association between the distribution of -308 TNF-α polymorphism and the risk of developing cervical cancer even after combining the data from the two ethnic populations (X2 = 2.26. In addition, using the chi-squared test we found no significant association between the known risk factors for cervical cancer and the allele distribution of -308 TNF-α. However, the frequency of the rare high-producing allele -308A of TNF-α was significantly lower in the South African population when compared to Caucasians and Chinese population groups. Conclusion We demonstrated no association between -308 TNF

  17. The VEGF and BMP-2 levels in patients with ankylosing spondylitis and the relationship to treatment with tumour necrosis factor alpha inhibitors.

    Science.gov (United States)

    Tošovský, Marian; Bradna, Petr; Andrýs, Ctirad; Andrýsová, Kateřina; Cermáková, Eva; Soukup, Tomáš

    2014-01-01

    Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum

  18. Regulation of human lung fibroblast C1q-receptors by transforming growth factor-beta and tumor necrosis factor-alpha.

    Science.gov (United States)

    Lurton, J; Soto, H; Narayanan, A S; Raghu, G

    1999-03-01

    Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are two polypeptide mediators which are believed to play a role in the evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of these two substances on the expression of receptors for collagen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen in human lung fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on C1q binding [Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells, referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF-alpha in serum-free conditions. The levels of mRNA were assessed by in situ hybridization and Northern analysis, and protein levels compared after SDS-polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF-beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively, whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA levels increased to a lesser extent in both cells. These increases were not reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels significantly. They also indicated different subsets of human lung fibroblasts respond differently to inflammatory mediators.

  19. Perbedaan Kadar Vitamin E dan Tumor Necrosis Factor Alpha (TNF-α berdasar atas Status Massa Lemak Pasien dalam Hemodialisis Kronik

    Directory of Open Access Journals (Sweden)

    Rudi Supriadi

    2017-10-01

    Difference between Vitamin E and Tumor Necrosis Factor Alpha (TNF-α Levels based on Fat Mass Status in Chronic Hemodialysis Patients Malnutrition-inflammation syndrome is a problem frequently found in patients who undergo chronic hemodialysis (HD. Increased level of inflammation has a higher risk for malnutrition. Fat mass shows better nutritional status changes in HD patients. TNF-α will cause increased ROS production and will be scavenged by vitamin E that are both saved in fat mass. This study aimed to determine the difference between vitamin E  and TNF-α levels in two fat mass groups of chronic HD patients. This study was a cross-sectional observational-analytic study on 42 male chronic HD patients at Dr. Hasan Sadikin General Hospital Bandung in the period of September–October 2016. Fat mass was measured by BIA and divided in two fat mass groups, higher and normal/lower mass groups. Vit E and TNF-α levels were measured by chromatography and ELISA. Non-paired groups difference test was used as the statistical analysis. The results showed a higher level of vitamin E in higher fat mass group than normal/lower group (p=0.042. TNF-α level tended to be lower in higher fat mass group than in the normal/lower group;  however, the difference was not significant statistically (p=0.443. Subjects who were  >55 years showed a higher level of vitamin E in hifher fat mass group than in normal/lower (p=0.029. The higher fat mass group with HD duration  >24 months showed lower vitamin E level than those with the HD duration ≤24 months (p=0.005. Normal/lower fat mass group with a HD duration of  >24 months showed a higher TNF-α level than≤24 months(p=0.031. In conclusion, in chronic HD patients the vitamin E level is higher in the higher fat mass group than in the normal/lower group. The vitamin E level in the higher fat mass with HD duration of  >24 months is lower than in the HD duration of  ≤24 months. There is no significant difference in TNF-α level

  20. Lung toxicity of hard metal particles and production of interleukin-1, tumor necrosis factor-alpha, fibronectin, and cystatin-c by lung phagocytes.

    Science.gov (United States)

    Huaux, F; Lasfargues, G; Lauwerys, R; Lison, D

    1995-05-01

    Hard metal alloys (WC-Co) are made of a mixture of cobalt (Co; 6%) and tungsten carbide (WC; 94%) particles. Chronic inhalation of hard metal dust can lead to the development of a fibrosing alveolitis, the pathogenesis of which is still undefined. The present investigation was undertaken to assess the effect of Co, WC, and WC-Co particles on the release by lung phagocytes of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), fibronectin, and cystatin-c. The responses were compared with those induced by two other lung toxicants, i.e., crystalline silica (DQ12) and arsenic trioxide (As2O3). IL-1 and TNF-alpha activities produced in the presence and absence of LPS stimulation were measured with the aid of bioassays while fibronectin and cystatin-c were determined by latex immunoassays. In vitro, maximal noncytotoxic doses of As2O3, Co, WC, or WC-Co did not significantly affect the production of these mediators by rat alveolar macrophages. In contrast, DQ12 enhanced the production of TNF-alpha (with and without LPS stimulation) and IL-1 (after LPS stimulation) and decreased cystatin-c release (in the absence of LPS). Following a single intratracheal instillation of the different test preparations in the rat, the response of the lung phagocytes obtained by bronchoalveolar lavage (BAL) 24 hr later was examined. We were unable to detect any consistent effect of Co (0.06 mg/100 g body wt), WC (1 mg/100 g body wt), or WC-Co treatment (1 mg/100 g body wt) on the production of the above mediators. In contrast, after LPS stimulation, As2O3 (0.5 mg/100 g body wt) and DQ12 (1 mg/100 g body wt) stimulated the production of TNF-alpha and IL-1. In the absence of LPS, As2O3 stimulated fibronectin and cystatin-c production and DQ12 stimulated cystatin-c release. Since the dose of WC-Co used in vivo (1 mg/100 g body wt) caused pronounced lung inflammation (increased LDH, protein, and albumin levels in BAL fluid), we conclude that the acute lung toxicity of WC-Co particles

  1. The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in South African women with cervical cancer and control women

    International Nuclear Information System (INIS)

    Govan, Vandana A; Constant, Debbie; Hoffman, Margaret; Williamson, Anna-Lise

    2006-01-01

    Cervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV). Although the incidence of genital HPV infection in various population groups is high, most of these regress without intervention. Investigating genetic host factors and cellular immune responses, particularly cytokines, could help to understand the association between genital HPV infection and carcinogenesis. The tumor necrosis factor alpha (TNF-α) cytokine plays an important role in all stages of cervical cancer and has the ability to induce the regression of human tumors. Therefore the aim of the study was to investigate the allelic distribution of -308 TNF-α gene polymorphism in South African women with cervical cancer compared to control women. Included in our study were women with histologically proven cancer of the cervix (n = 244) and hospital-based controls (n = 228). All patients and controls were from mixed race and black population groups in South Africa. The detection of a bi-allelic -308 (A/G) polymorphism in the promoter region of TNF-α was investigated using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The distributions of the allelic frequencies were stratified in both patients and controls into two South African ethnic population groups. In this study we observed no association between the distribution of -308 TNF-α polymorphism and the risk of developing cervical cancer even after combining the data from the two ethnic populations (X 2 = 2.26). In addition, using the chi-squared test we found no significant association between the known risk factors for cervical cancer and the allele distribution of -308 TNF-α. However, the frequency of the rare high-producing allele -308A of TNF-α was significantly lower in the South African population when compared to Caucasians and Chinese population groups. We demonstrated no association between -308 TNF-α polymorphism and the risk of cervical cancer among two

  2. Comparison of CCL28, interleukin-8, interleukin-1β and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis.

    Science.gov (United States)

    Ertugrul, A S; Sahin, H; Dikilitas, A; Alpaslan, N; Bozoglan, A

    2013-02-01

    Cytokines produced by various cells are strong local mediators of inflammation. Mucosa-associated epithelial chemokine (CCL28), interleukin-8 (IL-8), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) are major cytokines that play important roles in the periodontal inflammatory process. In this study we aimed to compare the levels of CCL28, IL-8, IL-1β and TNF-α in the gingival crevicular fluid of both periodontally healthy subjects and in subjects diagnosed with gingivitis, chronic periodontitis and generalized aggressive periodontitis. A total of 84 subjects participated in the study: 21 subjects had gingivitis, 21 subjects had chronic periodontitis, 21 subjects had generalized aggressive periodontitis and 21 were periodontally healthy. The levels of CCL28, IL-8, IL-1β and TNF-α were analyzed using enzyme-linked immune sorbent assay (ELISA). The total levels of CCL28 and IL-8 in the gingival crevicular fluid of the generalized aggressive periodontitis group (324.74 ± 42.62 pg/30 s, 487.62 ± 49.21 pg/30 s) were significantly higher than those of the chronic periodontitis group (268.81 ± 28.64 pg/30 s, 423.65 ± 35.24 pg/30 s), the gingivitis group (146.35 ± 17.46 pg/30 s, 310.24 ± 48.20 pg/30 s) and the periodontally healthy group (92.46 ± 22.04 pg/30 s, 148.41 ± 24.64 pg/30 s). Similarly, the total levels of IL-1β and TNF-α in the generalized aggressive periodontitis group (110.23 ± 9.20 pg/30 s, 1284.46 ± 86.32 pg/30 s) were significantly higher than those in the chronic periodontitis group (423.65 ± 35.24 pg/30 s, 82.64 ± 9.12 pg/30 s), the gingivitis group (52.10 ± 7.15 pg/30 s, 824.24 ± 44.68 pg/30 s) and the periodontally healthy group (36.44 ± 8.86 pg/30 s, 628.26 ± 34.61 pg/30 s). CCL28, IL-8, IL-1β and TNF-α may play key roles in the host response to inflammation in periodontal diseases. As the severity of periodontal diseases increases, destruction of periodontal tissues also increases. Inflammation is one among

  3. [Association of occupational chronic psychological stress with heat shock protein 70 in serum and tumor necrosis factor-alpha expression levels].

    Science.gov (United States)

    Qiu, F Y; Tian, R L; Qiang, Y; He, K P; Liu, H R; Zhang, W; Song, H

    2016-05-01

    To investigate the relationship between occupational chronic psychological stress with heat shock protein 70 (HSP70) and tumor necrosis factor-alpha (TNF-α). Using case-control study design, we selected 622 cases in 20 to 60 years old and unrelated patients with metabolic syndrome as the case group between October 2011 and October 2012 at two hospitals of Ningxia hui autonomous region. At the same time, we selected 600 healthy people from health check-up crowd in the above two hospitals as control group. The the research objects were sex, age, nation, height, weight, smoking, drinking, exercise, and so on. After informed consent, all the research objects were collected fasting venous blood samples 10 ml in order to proceed laboratory testing of biochemical indicators. The expression of HSP70 and TNF-α in serum was determined by ELISA. Using the revised occupational stress inventory (OSI) to survey the occupational chronic psychological stress factors and stress level of research object. The correlation of occupational chronic psychological stress scores with HSP70 and TNF-α was investigated by partial correlation analysis. We built a multivariate linear regression equation With HSP70 and TNF alpha as the independent variable and occupational chronic psychological stress scores as the dependent variable, using equation of the determination coefficient R(2) to judge the degree of fitting equation. The total points of chronic stress factors in all respondents was (136.65±16.19). Among them, the mild stress level group was 313, moderate was 588, severe was 321, chronic heart stress factors scores were (119.96±13.30), (135.33±3.23), (155.33±13.55) points, respectively. In the case group subjects, the expression of HSP70 in mild, moderate and severe occupational chronic psychological stress levels were (29.88±30.08), (36.38±30.08), (27.16±23.77) ng/ml (F=6.85, P=0.001). The control group were (27.64±9.89), (39.78±29.77), (3.94±3.09) ng/ml (F=125

  4. The ubiquitous interleukin-6: a time for reappraisal

    Directory of Open Access Journals (Sweden)

    Fisman Enrique Z

    2010-10-01

    Full Text Available Abstract Interleukin-6 (IL-6 is a multifunctional cytokine regulating humoral and cellular responses and playing a central role in inflammation and tissue injury. Its effects are mediated through interaction with its receptor complex, IL-6Rβ (also known as gp130. It plays an important role in the pathogenesis of coronary artery disease and large quantities of IL-6 are found in human atherosclerotic plaques. IL-6 levels positively correlate with higher all-cause mortality, unstable angina, left ventricular dysfunction, propensity to diabetes and its complications, hypertension, obesity and several types of cancer. IL-6 levels augmentation demonstrates a remarkable parallel with another biomarkers reflecting harmful processes, like tumor necrosis factor alpha, interleukins 8 and 18, YKL-40, C reactive protein and resistin. Due to these facts, IL-6 was classified as a noxious interleukin. Nonetheless, there are several facts that challenge this usually accepted point of view. Since IL-6 has also anti-inflammatory activity, it seems reasonable to assume that favorable aspects exist. These aspects are two: 1. protection against bacterial infections, inactivating proinflammatory mediators, mitigating the course of septic shock and inducing the production of cortisol; and 2. influence on insulin sensitivity during exercise; this aspect is even more important. During exercise IL-6 is synthesized and released by muscles, with enhanced insulin action immediately at early recovery. Skeletal muscle may be considered as an endocrine organ; contracting muscles produce IL-6 and release it into the blood exerting its effects on other organs. The increase in circulating levels of IL-6 after exercise is consistent and proportional to exercise duration, intensity, muscle mass involved and endurance capacity. Thus, the fascinating possibility that the plenteous beneficial health effects of exercise could be ultimately mediated by IL-6 merits further elucidation

  5. Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men.

    Science.gov (United States)

    Chennaoui, M; Sauvet, F; Drogou, C; Van Beers, P; Langrume, C; Guillard, M; Gourby, B; Bourrilhon, C; Florence, G; Gomez-Merino, D

    2011-11-01

    Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances. To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29±3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (Pstressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide

    DEFF Research Database (Denmark)

    Bendtzen, K; Morling, N; Fomsgaard, A

    1988-01-01

    The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysaccharide-activated mononuclear cells from 39 healthy donors was studied in vitro by bioassay and ELISA. The donors were typed for HLA-A, -B, -C, -DR, and -DP antigens. There was no detectable production of TNF beta...

  7. Role of nitric oxide in recombinant tumor necrosis factor-alpha-induced circulatory shock : A study in patients treated for cancer with isolated limb perfusion

    NARCIS (Netherlands)

    Zwaveling, JH; Maring, JK; Moshage, H; vanGinkel, RJ; Hoekstra, HJ; Donse, IF; Girbes, ARJ; Schraffordt Koops, H.

    1996-01-01

    Objectives: To analyze the mechanism of vasodilation and circulatory shock occurring in patients who are treated with isolated limb perfusion with melphalan and recombinant tumor necrosis factor (TNF)-alpha for locally advanced malignant tumors, To determine the role of nitric oxide, if any, by

  8. Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide

    DEFF Research Database (Denmark)

    Bendtzen, K; Morling, N; Fomsgaard, A

    1988-01-01

    The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysaccharide-activated mononuclear cells from 39 healthy donors was studied in vitro by bioassay and ELISA. The donors were typed for HLA-A, -B, -C, -DR, and -DP antigens. There was no detectable production of TNF be...

  9. The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment

    DEFF Research Database (Denmark)

    Björkman, Lena; Mårtensson, Jonas; Winther, Malene

    2016-01-01

    by tumor necrosis factor alpha (TNF-α) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin A-treated neutrophils, but no reactivation......Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca(2......+), and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils. This response was largely increased...

  10. Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease

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    Tetsuya Ishida

    2014-01-01

    Full Text Available We report a 45-year-old female patient who developed acute hepatic disorder during anti-tumor necrosis factor α therapy for the treatment of Crohn's disease (CD. She was diagnosed as colonic CD and placed on infliximab (IFX. She was negative for hepatitis B surface antigen at the initiation of IFX therapy, but developed acute hepatitis after the 30th administration of IFX 4 years and 1 month after the first administration. She was suspected to have had occult hepatitis B virus infection before IFX therapy, and de novo hepatitis B was considered the most likely diagnosis. Hepatitis subsided after discontinuation of anti-tumor necrosis factor α therapy and initiation of treatment with entecavir. She started to receive adalimumab to prevent relapse of CD. She has continued maintenance therapy with entecavir and adalimumab and has since been asymptomatic. As de novo hepatitis B may be fatal, virological testing for hepatitis B is essential for patients who are being considered for treatment that may weaken the immune system.

  11. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1.

    Science.gov (United States)

    Damgaard, C; Kantarci, A; Holmstrup, P; Hasturk, H; Nielsen, C H; Van Dyke, T E

    2017-04-01

    Porphyromonas gingivalis is regarded as a significant contributor in the pathogenesis of periodontitis and certain systemic diseases, including atherosclerosis. P. gingivalis occasionally translocates from periodontal pockets into the circulation, where it adheres to red blood cells (RBCs). This may protect the bacterium from contact with circulating phagocytes without affecting its viability. In this in vitro study, we investigated whether human peripheral blood neutrophils from 10 subjects with localized aggressive periodontitis (LAgP) and 10 healthy controls release the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor α (TNF-α), the chemokine (C-X-C motif) ligand 8 (CXCL8; also known as IL-8) and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemotactic protein-1) and intracellular reactive oxygen species (ROS) in response to challenge with P. gingivalis. In addition, the impact of RBC interaction with P. gingivalis was investigated. The actions of resolvin E1 (RvE1), a known regulator of P. gingivalis induced neutrophil responses, on the cytokine and ROS responses elicited by P. gingivalis in cultures of neutrophils were investigated. Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant in both groups, but reduced the generation of ROS in the group of healthy controls, and showed a similar tendency in the group of subjects with LAgP. RvE1 had no impact on the production of intracellular ROS, TNF-α, IL-6, CXCL8 and CCL2 by neutrophils from either group, but tended to reduce the generation of ROS in subjects with LAgP in the absence of RBCs. Our data support that binding to RBCs protects P. gingivalis from ROS and concomitantly enhances neutrophil release of proinflammatory cytokines providing a selective

  12. Ketamine inhibits tumor necrosis factor-α and interleukin-6 gene expressions in lipopolysaccharide-stimulated macrophages through suppression of toll-like receptor 4-mediated c-Jun N-terminal kinase phosphorylation and activator protein-1 activation

    International Nuclear Information System (INIS)

    Wu, G.-J.; Chen, T.-L.; Ueng, Y.-F.; Chen, R.-M.

    2008-01-01

    Our previous study showed that ketamine, an intravenous anesthetic agent, has anti-inflammatory effects. In this study, we further evaluated the effects of ketamine on the regulation of tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) gene expressions and its possible signal-transducing mechanisms in lipopolysaccharide (LPS)-activated macrophages. Exposure of macrophages to 1, 10, and 100 μM ketamine, 100 ng/ml LPS, or a combination of ketamine and LPS for 1, 6, and 24 h was not cytotoxic to macrophages. A concentration of 1000 μM of ketamine alone or in combined treatment with LPS caused significant cell death. Administration of LPS increased cellular TNF-α and IL-6 protein levels in concentration- and time-dependent manners. Meanwhile, treatment with ketamine concentration- and time-dependently alleviated the enhanced effects. LPS induced TNF-α and IL-6 mRNA syntheses. Administration of ketamine at a therapeutic concentration (100 μM) significantly inhibited LPS-induced TNF-α and IL-6 mRNA expressions. Application of toll-like receptor 4 (TLR4) small interfering (si)RNA into macrophages decreased cellular TLR4 levels. Co-treatment of macrophages with ketamine and TLR4 siRNA decreased the LPS-induced TNF-α and IL-6 productions more than alone administration of TLR4 siRNA. LPS stimulated phosphorylation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos from the cytoplasm to nuclei. However, administration of ketamine significantly decreased LPS-induced activation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos. LPS increased the binding of nuclear extracts to activator protein-1 consensus DNA oligonucleotides. Administration of ketamine significantly ameliorated LPS-induced DNA binding activity of activator protein-1. Therefore, a clinically relevant concentration of ketamine can inhibit TNF-α and IL-6 gene expressions in LPS-activated macrophages. The suppressive mechanisms occur through suppression of TLR4-mediated

  13. Role of cytokine gene (interferon-γ, transforming growth factor-β1, tumor necrosis factor-α, interleukin-6, and interleukin-10 polymorphisms in the risk of oral precancerous lesions in Taiwanese

    Directory of Open Access Journals (Sweden)

    Han-Jen Hsu

    2014-11-01

    Full Text Available Oral squamous cell carcinoma can be preceded by some benign oral lesions with malignant potential, including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis. There are different degrees of inflammatory cells infiltration in histopathology. Inflammatory cytokines may play a pathogenic role in the development of oral precancerous lesions (OPCLs. Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. We hypothesized that the risk of OPCLs might be associated with cytokine gene polymorphisms of interferon (IFN-γ, transforming growth factor (TGF-β1, tumor necrosis factor (TNF-α, interleukin (IL-6, and IL-10. In the present study, 42 OPCL patients and 128 controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A, TGF-β1 (codons 10 T/C and 25 G/C, TNF-α (−308 G/A, IL-6 (−174 G/C, and IL-10 (−1082 A/G, –819 T/C, and −592 A/C]. Cytokine genotyping was determined by the polymerase chain reaction sequence-specific primer technique using commercial primers. Allele and genotype data were analyzed for significance of differences between cases and controls using the Chi-square (χ2 test. Two-sided p < 0.05 were considered to be statistically significant. A series of multivariate logistic regression models, adjusted for age, sex, betel quid chewing, alcohol consumption, and smoking, was constructed in order to access the contribution of homozygous or heterozygous variant genotypes of polymorphisms. The TNF-α (−308 polymorphism was significantly associated with OPCLs. There were significant differences in the distribution of AA, GA, and GG genotypes between OPCL patients and controls (p = 0.0004. Patients with the AA or GA genotype had a 3.63-fold increased risk of OPCLs. The TGF-β1 (codon 10 and 25 polymorphism was also significantly associated with OPCLs (p < 0.001. The IL-6 polymorphism was significantly associated with OPCLs

  14. Analysis of polymorphisms of tumor necrosis factor-alpha and polymorphic xenobiotic metabolizing enzymes in inflammatory bowel disease: study from northern India.

    Science.gov (United States)

    Mittal, Rama D; Manchanda, Parmeet K; Bid, Hemant K; Ghoshal, Uday C

    2007-06-01

    Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine associated with inflammatory diseases, while GSTM1 and T1 enzymes catalyze detoxification of products of oxidative stress and hence reduce inflammation. Thus, both may play important roles in the pathogenesis of inflammatory bowel disease (IBD). The present study aimed to evaluate the effect of polymorphism of the TNF-alpha promoter at the -308 site, GSTM1 and GSTT1 in patients with IBD and healthy controls from northern India. Genotyping was performed in 114 patients with IBD (22 Crohn's disease [CD] and 92 ulcerative colitis [UC]) in TNF-alpha and 105 (20 CD and 85 UC) in GSTM1 and T1 and 164 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR methods. Patients with IBD were comparable to healthy controls in relation to age and gender. Genotypic and allelic frequencies of TNF-alpha were comparable among patients with IBD and healthy controls. GSTM1 null genotype was more frequent in UC than in healthy controls (52/85 vs 49/164; P GST genotypes further increases the risk, possibly due to gene-gene interaction. TNF-alpha is unlikely to be an important determinant of susceptibility to IBD in the Indian population.

  15. Tumor necrosis factor-alpha and angiostatin are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome.

    Science.gov (United States)

    Hamacher, Jürg; Lucas, Rudolf; Lijnen, H Roger; Buschke, Susanne; Dunant, Yves; Wendel, Albrecht; Grau, Georges E; Suter, Peter M; Ricou, Bara

    2002-09-01

    Acute respiratory distress syndrome (ARDS) is characterized by an extensive alveolar capillary leak, permitting contact between intra-alveolar factors and the endothelium. To investigate whether factors contained in the alveolar milieu induce cell death in human lung microvascular endothelial cells, we exposed these cells in vitro to bronchoalveolar lavage fluid (BALF) supernatants from control patients, patients at risk of developing ARDS, and patients with early- and late-phase ARDS. In contrast to BALF from control patients, a significant cytotoxicity was found in BALF from patients at risk of developing ARDS, with late-phase ARDS, and especially from patients with early-phase ARDS. Subsequently, we determined the levels of factors known to exert cytotoxicity in endothelial cells, i.e., tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and angiostatin. BALF from patients at risk of developing ARDS, with early-phase ARDS, and with late-phase ARDS, contained increased levels of TNF-alpha and angiostatin, but not of TGF-beta1, as compared with BALF from control patients. Whereas inhibition of TGF-beta1 had no effect in this setting, neutralization of TNF-alpha or angiostatin inhibited the cytotoxic activity on endothelial cells of part of the early-phase ARDS BALF. These results indicate that TNF-alpha and angiostatin may contribute to ARDS-related endothelial injury.

  16. Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy.

    Science.gov (United States)

    Hlavaty, T; Krajcovicova, A; Letkovsky, J; Sturdik, I; Koller, T; Toth, J; Huorka, M

    2016-01-01

    Relapse rates after discontinuing anti-tumor necrosis factor-α (TNFα) therapy of inflammatory bowel disease (IBD) patients in deep remission are poorly understood. This prospective single-center open-label study evaluated the relapse rates of IBD patients after stopping anti-TNFα therapy. All IBD patients who were in clinical remission and stopped anti-TNFα therapy in 2011-2013 and were followed up for at least 12 months were enrolled. The "Ultradeep" patients were in calprotectin-negative (risk factors identified. One year after stopping, 27 % and 27 % of the Ultradeep (n = 11) and Clinical (n = 11) patients relapsed, respectively. Two years after stopping, 57 % and 62 % relapsed, respectively (p = 0.89). All relapsed patients who underwent retreatment with anti-TNFα therapy re-entered remission. Male sex was a significant risk factor for relapse (p = 0.03). Our study showed that even highly selected IBD patients who lack clinical, endoscopic or laboratory signs of disease activity have a relatively high relapse rate in the follow-up period after ceasing anti-TNFα therapy (Tab. 2, Fig. 3, Ref. 24).

  17. The Effect of Aerobic Training and Arbotin on Cardiac Nitric Oxide, Tumor Necrosis Factor alpha, and Vascular Endothelial Growth Factor in Male Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Rahemeh Jahangiri Jahangiri

    2017-07-01

    Full Text Available Background and Objectives: Diabetes is one of the most important metabolic diseases, which its incidence rate has increased in recent years. In this disease, the insulin function is impaired, leading to several complications. Physical exercise and medicinal plants are considered as a way to control diabetes along with nutrition and medicine. The present study was conducted with the purpose of determining the effect of aerobic training and use of arbutin on cardiac nitric oxide, tumor necrosis factor-α and vessel endothelial growth factor in male diabetic rats. Methods: In this experimental study, 42 male adult Wistar rats (age, 8 weeks; weight, 190-220g, were randomly divided into 6 groups of 7 each (control, arbutin, diabetic, diabetic+training, diabetic+arbutin, and diabetic+training+arbutin. Training programs included 5 days of swimming per week for 6 weeks. Sampling from the heart was performed 72 hours after the last training session and arbutin consumption to analyze NO, TNF-α and VEGF. Data were analyzed using one-way ANOVA at the significance level p≤0.05. Results: Aerobic training along with use of arbutin led to increased levels of NO and VEGF and decreased level of TNF-α in cardiac tissue of diabetic rats (p<0.001. Conclusion: The results indicated that a period of regular aerobic training and use of arbutin can be considered as an appropriate non-medicinal method to control diabetes mellitus type 2 through decrease in inflammatory factors.

  18. Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor. alpha. : Relevance to genetic predisposition to systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, C.O.; Fronek, Z.; Koo, M.; McDevitt, H.O. (Stanford Univ. School of Medicine, CA (USA)); Lewis, G.C. (Genentech Inc., San Francisco, CA (USA)); Hansen, J.A. (Fred Hutchinson Cancer Research Center, Seattle, WA (USA))

    1990-02-01

    The authors report on the production of tumor necrosis factor (TNF)-{alpha} and TNF-{beta} by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-{alpha}, whereas DR3- and DR4-positive subjects show high levels of TNF-{alpha} production. No correlation between TNF-{alpha} levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-{alpha} inducibility; this genotype is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-{alpha} production. DR4 haplotype is associated with high TNF-{alpha} inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.

  19. Tributyltin (TBT) and Dibutyltin (DBT) Alter Secretion of Tumor Necrosis Factor Alpha (TNFα) from Human Natural Killer (NK) Cells and a Mixture of T cells and NK Cells

    Science.gov (United States)

    Hurt, Kelsi; Hurd-Brown, Tasia; Whalen, Margaret

    2012-01-01

    Butyltins (BTs) have been in widespread use. Tributyltin (TBT) has been used as a biocide in a variety of applications and is found in human blood samples. Dibutyltin (DBT) has been used as a stabilizer in polyvinyl chloride plastics and as a de-worming agent in poultry. DBT, like TBT, is found in human blood. Human natural killer (NK) cells are the earliest defense against tumors and viral infections and secrete the cytokine tumor necrosis factor (TNF) alpha (α). TNFα is an important regulator of adaptive and innate immune responses. TNFα promotes inflammation and an association between malignant transformation and inflammation has been established. Previously, we have shown that TBT and DBT were able to interfere with the ability of NK cells to lyse tumor target cells. Here we show that BTs alter cytokine secretion by NK cells as well as a mixture of T and NK lymphocytes (T/NK cells). We examined 24 h, 48 h, and 6 day exposures to TBT (200- 2.5 nM) and DBT (5- 0.05 µM) on TNFα secretion by highly enriched human NK cells and T/NK cells. The results indicate that TBT (200 - 2.5 nM) decreased TNFα secretion from NK cells. In the T/NK cells 200 nM TBT decreased secretion while 100-5 nM TBT increased secretion of TNFα. NK cells or T/NK cells exposed to higher concentrations of DBT showed decreased TNFα secretion while lower concentrations showed increased secretion. The effects of BTs on TNFα secretion are seen at concentrations present in human blood. PMID:23047847

  20. Prevotella intermedia lipopolysaccharide stimulates release of tumor necrosis factor-alpha through mitogen-activated protein kinase signaling pathways in monocyte-derived macrophages.

    Science.gov (United States)

    Kim, Sung-Jo; Choi, Eun-Young; Kim, Eun Gyung; Shin, Su-Hwa; Lee, Ju-Youn; Choi, Jeom-Il; Choi, In-Soon

    2007-11-01

    The purpose of this study was to investigate the effects of lipopolysaccharide from Prevotella intermedia, a major cause of inflammatory periodontal disease, on the production of tumor necrosis factor (TNF)-alpha and the expression of TNF-alpha mRNA in differentiated THP-1 cells, a human monocytic cell line. The potential involvement of the three main mitogen-activated protein kinase (MAPK) signaling pathways in the induction of TNF-alpha production was also investigated. Lipopolysaccharide from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. It was found that P. intermedia lipopolysaccharide can induce TNF-alpha mRNA expression and stimulate the release of TNF-alpha in differentiated THP-1 cells without additional stimuli. Treatment of the cells with P. intermedia lipopolysaccharide resulted in a simultaneous activation of three MAPKs [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and p38]. Pretreatment of the cells with MAPK inhibitors effectively suppressed P. intermedia lipopolysaccharide-induced TNF-alpha production without affecting the expression of TNF-alpha mRNA. These data thus provided good evidence that the MAPK signaling pathways are required for the regulation of P. intermedia lipopolysaccharide-induced TNF-alpha synthesis at the level of translation more than at the transcriptional level.

  1. Anti-tumor Necrosis Factor Alpha (Infliximab) Attenuates Apoptosis, Oxidative Stress, and Calcium Ion Entry Through Modulation of Cation Channels in Neutrophils of Patients with Ankylosing Spondylitis.

    Science.gov (United States)

    Ugan, Yunus; Nazıroğlu, Mustafa; Şahin, Mehmet; Aykur, Mehmet

    2016-08-01

    Ankylosing Spondylitis (AS) is known to be associated with increased neutrophil activation and oxidative stress, however, the mechanism of neutrophil activation is still unclear. We have hypothesized that the antioxidant and anti-tumor necrosis factor properties of infliximab may affect intracellular Ca(2+) concentration in the neutrophils of AS patients. The objective of this study was to investigate the effects of infliximab on calcium signaling, oxidative stress, and apoptosis in neutrophils of AS patients. Neutrophils collected from ten patients with AS and ten healthy controls were used in the study. In a cell viability test, the ideal non-toxic dose and incubation time of infliximab were found as 100 μM and 1 h, respectively. In some experiments, the neutrophils were incubated with the voltage-gated calcium channel (VGCC) blockers verapamil + diltiazem (V + D) and the TRPM2 channel blocker 2-aminoethyl diphenylborinate (2-APB). Intracellular Ca(2+) concentration, lipid peroxidation, apoptosis, caspase 3, and caspase 9 values were high in neutrophils of AS patients and were reduced with infliximab treatment. Reduced glutathione level and glutathione peroxidase activity were low in the patients and increased with infliximab treatment. The intracellular Ca(2+) concentrations were low in 2-APB and V + D groups. In conclusion, the current study suggests that infliximab is useful against apoptotic cell death and oxidative stress in neutrophils of patients with AS, which seem to be dependent on increased levels of intracellular Ca(2+) through activation of TRPM2 and VGCC.

  2. Interleukin-6 Detection with a Plasmonic Chip

    Science.gov (United States)

    Tawa, Keiko; Sumiya, Masashi; Toma, Mana; Sasakawa, Chisato; Sujino, Takuma; Miyaki, Tatsuki; Nakazawa, Hikaru; Umetsu, Mitsuo

    Interleukin-6, a cytokine relating inflammatory and autoimmune activity, was detected with three fluorescence assays using a plasmonic chip. In their assays, the way of surface modification, sample volume, incubation time and mixing solution, were found to influence the detection sensitivity. When the assay was revised in the point of a rapid and easy process, the detection sensitivity was not compromised compared to assays with sufficient sample volume and assay time. To suit the purpose of immunosensing, the assay conditions should be determined.

  3. DEVELOPMENT OF ALOPECIA DURING TREATMENT WITH A TUMOR NECROSIS FACTOR-ALPHA INHIBITOR IN A FEMALE PATIENT WITH PSORIATIC ARTHRITS: A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    R. G. Mukhina

    2016-01-01

    Full Text Available Objective: to describe a case of the total development of alopecia in a female patient with psoriatic arthritis during treatment with a tumor necrosis factor-αlpha (TNF-α inhibitor. Materials and methods. Patient I., aged 36 years has been followed up at the Kazan’ Center of Rheumatic Diseases and Osteoporosis since 1998. At approximately the same time, the patient noted the appearance of skin eruptions behind the ears, on the skin of the scalp. She was examined by a dermatologist who diagnosed psoriasis. In 2005, she was admitted to Kazan’ Rheumatology Center, City Clinical Hospital Seven, for the development of obvious synovitis of the knee joint and for the inefficiency of therapy with nonsteroidal anti-inflammatory drugs and diagnosed with psoriatic arthritis. During the prescribed therapy with methotrexate 10 mg/week, evident menstrual irregularities were observed in the patient who stopped using the drug herself. The second pregnancy occurred in 2008. Articular syndrome progression and eruptive psoriasis were recorded in the lactation period. After lactation cessation in 2009, she was hospitalized again. Her examination revealed high laboratory activity (erythrocyte sedimentation rate, as high as 40 mm/hr; magnetic resonance imaging of the knee joints showed the signs of bilateral synovitis; lumbar spine radiography exhibited grade II sacroiliitis. Leflunomide 20 mg/day was recommended as a basic drug. In 2012, the patient used leflunomide, her condition worsened; joint pain progressed; new joints were involved into the process, and cutaneous manifestations were aggravated. To verify a diagnosis and to choose therapy, the patient was referred to a consultation at the Moscow Research Institute of Rheumatology. Results. In connection with the high activity of the disease and with no response to the performed therapy, it was recommended to initiate therapy with biologics, such as infliximab, the drug of choice. Seven infliximab

  4. Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration

    Science.gov (United States)

    2011-01-01

    Introduction Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair. Methods A micro-wound assay was used to assess meniscal cell migration and proliferation in response to the following treatments for 0, 24, or 48 hours: 0 to 10 ng/mL IL-1, TNF-α, or TGF-β1, in the presence or absence of 10% serum. Proliferated and total cells were fluorescently labeled and imaged using confocal laser scanning microscopy and the number of proliferated, migrated, and total cells was determined in the micro-wound and edges of each image. Meniscal cell proliferation was also assessed throughout meniscal repair model explants treated with 0 or 10 ng/mL IL-1, TNF-α, or TGF-β1 for 14 days. At the end of the culture period, biomechanical testing and histological analyses were also performed. Statistical differences were assessed using an ANOVA and Newman-Keuls post hoc test. Results IL-1 and TNF-α decreased cell proliferation in both cell and tissue models of meniscal repair. In the presence of serum, TGF-β1 increased outer zone cell proliferation in the micro-wound and in the cross section of meniscal repair model explants. Both IL-1 and TNF-α decreased the integrative shear strength of repair and extracellular matrix deposition in the meniscal repair model system

  5. Investigating the Impacts of Preoperative Steroid Treatment on Tumor Necrosis Factor-Alpha and Duration of Extubation Time underwent Ventricular Septal Defect Surgery

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    H. Hakan Poyrazoğlu

    2016-04-01

    Full Text Available Background: Cardiopulmonary bypass is known to cause inflammatory events. Inflammation occurs due to many known important biological processes. Numerous mechanisms are known to be responsible for the development of inflammatory processes. Currently, there are many defined mediators as a tumor necrosis factor-α (TNF-α playing an active role in this process. Aims: This research was to investigate the effects of preoperative steroid use on inflammatory mediator TNF-α and on time to extubation postoperatively in ventricular septal defect patients undergoing cardiopulmonary bypass surgery. Study Design: Controlled clinical study. Methods: This study included 30 patients. These patients were assigned into two groups, each containing 15 patients. 5 micrograms/kg methylprednisolone was injected intravenously 2 hours before the surgery to Group I, whereas there was no application to the patients in Group II. TNF-α (pg/mL level was measured in arterial blood samples obtained at four periods including: the preoperative period (Pre TNF; at the 5th minute of cross-clamping (Per TNF; 2 hours after termination of cardiopulmonary bypass (Post TNF; and at the postoperative 24th hours in cardiovascular surgery intensive care unit (Post 24 h TNF. Results: The mean cross-clamp time was 66±40 and 55±27 minutes in Group I and Group II respectively. No significant difference was found between the groups in terms of cross-clamp time (p>0.05. The mean time to extubation was 6.1±2.3 hours in Group I and 10.6±3.4 hours in Group II. Group I extubation time was significantly shorter than Group II. Group I TNF-α levels at Post TNF and Post24h TNF was lower than Group II. These differences are also statistically significant (p<0.05. Conclusion: There is a strong indication that preoperative steroid treatment reduced the TNF-α level together with shortens duration of postoperative intubation and positively contributes to extubation in ventricular septal defect

  6. Polymorphism of tumor necrosis factor alpha (TNF-alpha gene promoter, circulating TNF-alpha level, and cardiovascular risk factor for ischemic stroke

    Directory of Open Access Journals (Sweden)

    Cui Guanglin

    2012-10-01

    Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α is one of the most typical pro-inflammatory cytokines with both beneficial and destructive properties for the central nervous system. Increasing evidences have demonstrated the important role of TNF-α in the development of ischemic stroke, but studies examining the possible association with stroke or direct functional effects of polymorphisms in TNF-α have been contradictory. Findings In this study, a 2-kb length of the proximal promoter of the TNF-α was screened and four polymorphisms were investigated in the case–control study. Our data confirmed the association between -308G/A variant with stroke in 1,388 stroke patients and 1,027 controls and replicated in an independent population of 961 stroke patients and 821 controls (odds ratio (OR = 1.34, 95% confidence interval (CI =1.02 to 1.77 and OR = 1.56, 95% CI = 1.09 to 2.23, respectively. To reconcile the association between polymorphisms and stroke and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of 15 published studies in an Asian population. Our results demonstrated an association between rs1800629 and ischemic stroke (OR = 1.43, 95% CI = 1.21 to 1.69. Another meta-analysis results of 14 studies demonstrated that ischemic stroke patients have higher serum TNF-α level than the control subjects (standardized mean difference (SMD = 2.33, 95% CI = 1.85 to 2.81. In vitro evaluation of potential interaction between variants of the TNF-α gene (−308G/A, -857C/T, and -1031T/C demonstrated that these three polymorphisms could interact together to determine the overall activity of the TNF-α gene. Conclusions These findings strongly implicate the involvement of TNF-α in the pathogenesis of stroke.

  7. Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-alpha blocker in the treatment of rheumatic diseases.

    Science.gov (United States)

    Kim, Yun Jung; Bae, Sang-Cheol; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae-Hyun; Kim, Tae Yeob; Sohn, Joo Hyun; Lee, Hye-Soon

    2010-02-01

    To assess the safety of anti-tumor necrosis factor (TNF-alpha) therapy in patients with rheumatic diseases in terms of the reactivation of potential hepatitis B virus (HBV) occult infection. Patients who had taken anti-TNF-alpha for the treatment of rheumatic diseases from January 2002 to May 2008 were included in the study. In this patient group, we retrospectively investigated a series of serum aminotransferase levels, HBV serologic status, the type of anti-TNF-alpha therapy, duration of the anti-TNF-alpha treatment, and concurrent use of hepatotoxic drugs. A total of 266 cases were documented using 3 serologic markers for HBV infection: HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), and HBV core IgG Ab (HBcAb). Of these, 8 cases had chronic hepatitis B (HBsAg+), 170 cases were HBcAb-negative, and 88 cases were identified as having potential HBV occult infections represented by HBsAg-negative and HBcAb-positive, irrespective of the status of the HBsAb. The frequency of clinically significant (> 2 times normal value) and persistent increase (> 2 consecutive tests) of aminotransferase levels was significantly higher in the group with a potential HBV occult infection compared to the HBcAb-negative group. In the multiple logistic regression analysis controlling for various potential confounding factors such as prophylactic anti-tuberculosis medication, methotrexate, nonsteroidal antiinflammatory drugs, and the type of anti-TNF-alpha therapy, only potential HBV occult infection was a significant risk factor for abnormal liver function test (LFT). All rheumatic patients who plan to take anti-TNF-alpha treatment should undergo a test for HBV serology, including HBcAb, and have a close followup with an LFT test during therapy. Further prospective studies for hepatitis B viral load using HBV-polymerase chain reaction in patients who are HbcAb positive are needed to identify whether the abnormal LFT comes from the reactivation of occult HBV infection.

  8. A Role for Protein Phosphatase 2A in Regulating p38 Mitogen Activated Protein Kinase Activation and Tumor Necrosis Factor-Alpha Expression during Influenza Virus Infection

    Directory of Open Access Journals (Sweden)

    Anna H. Y. Law

    2013-04-01

    Full Text Available Influenza viruses of avian origin continue to pose pandemic threats to human health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated cytokine levels when compared with the seasonal H1N1 virus. We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF-alpha through p38 mitogen activated protein kinase (MAPK. However, the detailed mechanisms of p38MAPK activation and TNF-alpha hyperinduction following influenza virus infections are not known. Negative feedback regulations of cytokine expression play important roles in avoiding overwhelming production of proinflammatory cytokines. Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1 and protein phosphatase type 2A (PP2A in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac infected with H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A inhibitor, p38MAPK phosphorylation and TNF-alpha production were further increased in the virus-infected macrophages. However, H9N2/G1 did not induce the expression of PP2A indicating that the activation of PP2A is not mediated by p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced PP2A activation in primary macrophages. Our results may provide new insights into the control of cytokine dysregulation.

  9. A novel T cell cytokine stimulates interleukin-6 in human osteoblastic cells.

    Science.gov (United States)

    Rifas, L; Avioli, L V

    1999-07-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by a heavy lymphocytic infiltration into the synovial cavity, resulting in the secretion of a variety of cytokines which ultimately leads to destruction of joint tissue. Among the infiltrating cells are activated T cells which produce specific cytokines capable of osteoclast progenitor cell expansion, fusion, and activation. Cultures of activated human T cells and human osteoblasts (hOBs) were used to study the possibility that lymphokines may act on osteoblasts to produce the osteoclastogenic factor interleukin-6 (IL-6). Purified T cells were activated with a combination of anti-CD3 and anti-CD28 antibodies, cocultured with hOBs in direct physical contact or separated by a transwell system, and conditioned media (CM) were assayed for IL-6 production. After a 72 h incubation period, activated T cell-hOB interaction resulted in a 100-fold increase of IL-6 production over basal levels. The immunosuppressant cyclosporine A (CsA) inhibited T cell tumor necrosis factor alpha and IL-6 production but did not inhibit the T cell induction of IL-6 from hOB. Assay of activated T-cell CM on hOB revealed that a soluble factor, not cell-cell contact, was the major inducer of IL-6. The induction of IL-6 mRNA by both activated T cell CM and CsA-treated activated T cell CM was confirmed by Northern blot analysis. Neutralizing antibodies to IL-13 and IL-17 did not affect IL-6 production. These findings suggest that activated T cells produce a novel, potent, IL-6 inducing factor that may be responsible for the bone loss observed in RA patients.

  10. Circulating interleukin-6 and tumor necrosis factor receptor-1 predict ...

    African Journals Online (AJOL)

    Toxic look, constipation, high fever, splenomegaly, increased CRP and ESR were significantly presented in patients who displayed resistance to drug therapy. Both IL-6 and TNF-R1 plasma levels were significantly higher in patients than in control children, and in resistant cases than in responsive cases (before and 5 days ...

  11. Circulating interleukin-6 and tumor necrosis factor receptor-1 predict ...

    African Journals Online (AJOL)

    EL-HAKIM

    INTRODUCTION. Typhoid fever, encountered in all parts of the world, is nowadays primarily found in countries where sanitary conditions are poor. It is considered to be one of the most important and under-reported diseases in the developing world. In some areas, it has been estimated that typhoid fever is responsible.

  12. Interleukin-6 and neopterin in renal transplant recipients: a longitudinal study

    NARCIS (Netherlands)

    Raasveld, M. H.; Bloemena, E.; Wilmink, J. M.; Surachno, S.; Schellekens, P. T.; ten Berge, R. J.

    1993-01-01

    Serum and urine interleukin-6 (IL-6) levels and serum neopterin/creatinine ratios were longitudinally studied in 86 renal transplant recipients until 4 months after transplantation. During acute rejection and acute tubular necrosis (ATN), serum and urine IL-6 levels were elevated compared to during

  13. Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients

    Directory of Open Access Journals (Sweden)

    Denise Maciel Carvalho

    2014-01-01

    Full Text Available Background. During dengue virus (DV infection, monocytes produce tumor necrosis factor alpha (TNF-α and nitric oxide (NO which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1 on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1 serum levels and innate immune response (TLR4 expression and TNF-α/NO production of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA, TNF-α production by peripheral blood mononuclear cells (PBMCs, and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF was detected compared to patients with dengue hemorrhagic fever (DHF. Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.

  14. Skin cancer associated with commonly prescribed drugs: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and statins -weighing the evidence.

    Science.gov (United States)

    Nardone, Beatrice; Orrell, Kelsey A; Vakharia, Paras P; West, Dennis P

    2018-02-01

    Skin cancers, including both malignant melanoma (MM) and nonmelanoma skin cancer (NMSC), are the most commonly diagnosed cancers in the US. The incidence of both MM and NMSC continues to rise. Areas covered: Current evidence for an association between four of the most commonly prescribed classes of drugs in the U.S. and risk for MM and NMSC is reported. Medline was searched (January 2000 to May 2017) for each drug in the classes and for 'basal cell carcinoma', 'squamous cell carcinoma', 'non-melanoma skin cancer', 'skin cancer' and 'melanoma'. Skin cancer risk information was reported for: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins). Expert opinion: Since skin cancer risk is associated with all four classes of these commonly prescribed drugs that represent nearly 20% of the Top 100 drugs in the U.S., these important findings warrant enhanced education, especially for prescribers and those patients at high risk for skin cancer.

  15. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2.

    Science.gov (United States)

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan

    2017-01-01

    Tumor necrosis factor alpha (TNFα) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNFα on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNFα stimulus. We observed that HepG2 cell revealed a higher resistance to TNFα-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNFα, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNFα/control ratio>2.0 or expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNFα might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNFα. Collectively, these findings indicate that TNFα alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells.

  16. The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura

    Directory of Open Access Journals (Sweden)

    Emel Okulu

    2011-09-01

    Full Text Available Objective: To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-α -308 G/A and transforming growth factor-beta 1 (TGF-β1 –915 G/C polymorphisms in the development and clinical progression of childhood ITP.Materials and Methods: In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP and 48 healthy controls were investigated via LightCycler® PCR analysis for TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms.Results: The frequency of TNF-α -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05. The frequency of TGF-β1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05. The risk of developing ITP and clinical progression were not associated with TNF-α -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249 or TGF-β1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755 polymorphisms. Conclusion: The frequency of TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease.

  17. Expression of tumor necrosis factor-alpha converting enzyme and matrix metalloproteinase-3 in proliferated synovium in a patient with synovitis-acne-pustulosis-hyperostosis-osteitis syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Komiya Koichiro

    2009-09-01

    Full Text Available Abstract Introduction Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO syndrome is a rare disorder. The etiology remains unknown and the treatment is still empirical. Synovitis is one of the major manifestations, but information on histopathological features is still lacking. In this case, we investigated the histopathological features of SAPHO syndrome synovitis. Case presentation We present the case of a 53-year-old Japanese woman with SAPHO syndrome accompanied by marked knee synovitis and palmoplantar pustulosis. We found abundant sterile joint fluid in the right knee, and a blood test showed abnormally high values of C-reactive protein (17.26 mg/dl and matrix metalloproteinase-3 (800 ng/ml. Arthroscopic surgery revealed marked proliferation of villous synovial tissues similar to rheumatoid arthritis and standard microscopic findings were also similar to rheumatoid arthritis. Furthermore, for the first time, we demonstrated by immunohistochemistry the expression of tumor necrosis factor-alpha (TNF-α converting enzyme, TNF-α and matrix metalloproteinase-3 in the proliferated synovial lining cells. After arthroscopic synovectomy, her knee symptoms immediately diminished and laboratory data (matrix metalloproteinase-3 and C-reactive protein normalized within 2 weeks of surgery. Conclusion We demonstrate the expression of TNF-α converting enzyme, TNF-α and matrix metalloproteinase-3 in SAPHO syndrome synovitis for the first time and also show, both macro- and microscopically, the similarity between SAPHO syndrome and rheumatoid arthritis synovitis. These new findings support the recently reported successful treatment of SAPHO syndrome with antirheumatic drugs, especially with anti-TNF-α agents.

  18. Anti-inflammatory effects of the butanolic fraction of Byrsonima verbascifolia leaves: Mechanisms involving inhibition of tumor necrosis factor alpha, prostaglandin E(2) production and migration of polymorphonuclear leucocyte in vivo experimentation.

    Science.gov (United States)

    Saldanha, Aline Aparecida; de Siqueira, João Máximo; Castro, Ana Hortência Fonsêca; de Azambuja Ribeiro, Rosy Iara Maciel; de Oliveira, Flávio Martins; de Oliveira Lopes, Débora; Pinto, Flávia Carmo Horta; Silva, Denise Brentan; Soares, Adriana Cristina

    2016-02-01

    The leaves of Byrsonima verbascifolia (Malpighiaceae) are traditionally used to treat various diseases including inflammatory conditions. The main goal of this study was to evaluate the in vivo anti-inflammatory activity of the polar constituents from the butanolic fraction of B. verbascifolia leaves (BvBF), as well as to investigate the mechanisms involved in the anti-inflammatory activity. The polar constituents were identified by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD–MS) and matrix-assisted laser desorption/ionization – time-of-flight mass spectrometry (MALDI-TOF MS) to obtain a complete chemical profile of the fraction. Forty-five compounds were detected in the BvBF by LC-DAD–MS/MS, including condensed tannins, phenolic acids, flavonoids (flavones and flavonols) and other compounds. In addition, several condensed tannins were identified by MALDI-MS/MS, which are composed predominantly by procyanidin units (PCY) and up to six flavan-3-ol units. The BvBF exhibited significant antioxidant and anti-inflammatory activities. The BvBF inhibited paw edema and polymorphonuclear (PMN) leukocyte migration to the footpad and pleural cavity induced by carrageenan. Furthermore, a minor dose (12.50 mg/kg) of BvBF effectively decreased tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) levels in the footpad. These findings suggest that the mechanism of the anti-inflammatory action in the BvBF is linked to the inhibition of the production of inflammatory mediators such as TNF-α and PGE2 and the PMN cell migration.

  19. Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

    Science.gov (United States)

    Hernandez-Pando, R; Orozco, H; Arriaga, K; Sampieri, A; Larriva-Sahd, J; Madrid-Marina, V

    1997-01-01

    A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages

  20. Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

    LENUS (Irish Health Repository)

    Dowdall, J F

    2012-02-03

    The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

  1. Interleukin-6, age, and corpus callosum integrity.

    Directory of Open Access Journals (Sweden)

    Brianne M Bettcher

    Full Text Available The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6 and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine, as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC integrity, fractional anisotropy (FA of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories.

  2. Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes.

    Science.gov (United States)

    Seldon, P M; Barnes, P J; Giembycz, M A

    1998-01-01

    Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor necrosis factor-alpha (TNF-alpha) generation by murine macrophages and hepatocytes are suppressed markedly by agents that elevate intracellular cAMP. Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series prostaglandins also attenuate the induction of the TNF-alpha gene in human monocytes in response to bacterial LPS. The mechanism of action of cAMP is unclear, but in the mouse, is believed to involve the generation of this anti-inflammatory cytokine, interleukin-10 (IL-10). In this article, we describe the results of studies designed to determine the extent to which IL-10 contributes to the suppression of TNF-alpha generation from LPS-stimulated human monocytes evoked by 8-bromo cyclic AMP (8-Br-cAMP), rolipram, salbutamol, and prostaglandin E2 (PGE2). LPS evoked a time- and concentration-dependent generation of TNF-alpha (t1/2 = 4.5 h; EC50 = 273 pg/mL), which was inhibited by exogenous human recombinant (h) IL-10 (IC50 = 124 pg/mL), and by rolipram (EC50 = 420 nM), 8-Br-cAMP (EC50 = 77 (microM), PGE2 (EC50 = 15 nM) and salbutamol (EC50 = 20 nM). In addition, 8-Br-cAMP, PGE2; and salbutamol (but not rolipram) augmented significantly LPS-induced IL-10 production (two-to-fivefold) under identical experimental conditions. Pretreatment of monocytes with an anti-IL-10 monoclonal antibody (MAb) that abolished the inhibitory action of a maximally effective concentration of exogenous hrIL-10, failed to attenuate the inhibitory effect of rolipram, PGE2, salbutamol, and 8-Br-cAMP. Anti-IL-10 was similarly inactive when the number of monocytes seeded was increased from 0.5 to 4 x 10(6)/mL or when measurements were made at 42 h post-LPS, a time when the concentration of IL-10 released was maximal. Collectively, these data suggest that in contrast to murine hepatocytes and macrophages, IL-10 does not mediate the inhibitory effect of cAMP-elevating drugs on TNF

  3. The MC160 Protein Expressed by the Dermatotropic Poxvirus Molluscum Contagiosum Virus Prevents Tumor Necrosis Factor Alpha-Induced NF-κB Activation via Inhibition of I Kappa Kinase Complex Formation

    Science.gov (United States)

    Nichols, Daniel Brian; Shisler, Joanna L.

    2006-01-01

    The pluripotent cytokine tumor necrosis factor alpha (TNF-α) binds to its cognate TNF receptor I (TNF-RI) to stimulate inflammation via activation of the NF-κB transcription factor. To prevent the detrimental effects of TNF-α in keratinocytes infected with the molluscum contagiosum virus (MCV), this poxvirus is expected to produce proteins that block at least one step of the TNF-RI signal transduction pathway. One such product, the MC160 protein, is predicted to interfere with this cellular response because of its homology to other proteins that regulate TNF-RI-mediated signaling. We report here that expression of MC160 molecules did significantly reduce TNF-α-mediated NF-κB activation in 293T cells, as measured by gene reporter and gel mobility shift assays. Since we observed that MC160 decreased other NF-κB activation pathways, namely those activated by receptor-interacting protein, TNF receptor-associated factor 2, NF-κB-inducing kinase, or MyD88, we hypothesized that the MC160 product interfered with I kappa kinase (IKK) activation, an event common to multiple signal transduction pathways. Indeed, MC160 protein expression was associated with a reduction in in vitro IKK kinase activity and IKK subunit phosphorylation. Further, IKK1-IKK2 interactions were not detected in MC160-expressing cells, under conditions demonstrated to induce IKK complex formation, but interactions between the MC160 protein and the major IKK subunits were undetectable. Surprisingly, MC160 expression correlated with a decrease in IKK1, but not IKK2 levels, suggesting a mechanism for MC160 disruption of IKK1-IKK2 interactions. MCV has probably retained its MC160 gene to inhibit NF-κB activation by interfering with signaling via multiple biological mediators. In the context of an MCV infection in vivo, MC160 protein expression may dampen the cellular production of proinflammatory molecules and enhance persistent infections in host keratinocytes. PMID:16378960

  4. Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells.

    Directory of Open Access Journals (Sweden)

    Siti Sarah Fazalul Rahiman

    Full Text Available Dynorphin 1-17, (DYN 1-17 opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1-17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65 nuclear translocation and the release of interleukin-1beta (IL-1β and tumor necrosis factor-alpha (TNF-α from lipopolysaccharide (LPS-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1-17 and a specific range of fragments, with the greatest reduction observed with DYN 1-7 at a low concentration (10 nM. Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not other DYN 1-17 N-terminal fragments (DYN 1-10 and 1-11 on NF-κB/p65 nuclear translocation. DYN 1-17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1-7 at low concentrations (1 nM and 10 pM. These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1-17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways.

  5. Adrenaline influences the release of interleukin-6 from murine pituicytes

    DEFF Research Database (Denmark)

    Christensen, J D; Hansen, E W; Frederiksen, C

    1999-01-01

    In this study, we examined the effect of adrenaline and interleukin-1beta on interleukin-6 secretion from cultured murine neurohypophyseal cells. Cells were cultured from neurohypophyses of 3- to 5-week-old mice and experiments were performed after 13 days in culture. Interleukin-6 was measured...... in 24-h samples using a sandwich fluoroimmunoassay. Unstimulated cells released 19+/-3 fmol interleukin-6/neurohypophysis/24 h (mean +/- S.E.M., n = 42). Adrenaline and interleukin-1beta increased the release of interleukin-6 from the cells in a concentration-dependent manner. Incubation with adrenaline...

  6. Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans

    NARCIS (Netherlands)

    Stouthard, J. M.; van der Poll, T.; Endert, E.; Bakker, P. J.; Veenhof, C. H.; Sauerwein, H. P.; Romijn, J. A.

    1994-01-01

    Cytokines, such as tumor necrosis factor-alpha and interleukin-1 beta (IL-1 beta), alter thyroid hormone metabolism, and may be involved in the pathogenesis of the euthyroid sick syndrome. Both cytokines also induce the production of IL-6. To assess whether IL-6 itself modulates thyroid hormone

  7. Regulation of interleukin-6 secretion in murine pituicytes

    DEFF Research Database (Denmark)

    Thorn, Anders; Tuxen, Mikkel; Moesby, Lise

    2005-01-01

    -gamma on interleukin-6 secretion was not affected by the specific inducible nitric oxide synthase inhibitor 1400W (N-(3-[aminomethyl]benzyl)acetamidine). Furthermore interferon-gamma dose dependently inhibits unstimulated interleukin-6 secretion. Use of the nitric oxide releaser DETA/NO (2,2'-(hydroxynitrosohydrazono...

  8. Serum levels of interleukin-6, tumor necrosis factor-alpha and interferon-gama in infants with and without dengue Níveis séricos de interleucina-6, fator de necrose tumoral-alfa e interferon-gama em crianças menores de um ano com e sem dengue

    Directory of Open Access Journals (Sweden)

    Berta Nelly Restrepo

    2008-02-01

    Full Text Available This study compared the serum levels of IL-6, TNF-alpha and IFN-gamma, in children under 1 year of age with and without dengue. Sera were collected from a total of 41 children living in the Department of Antioquia, Colombia (27 patients with dengue and 14 controls. The results showed higher cytokine levels in children with dengue than without dengue, with statistically significant differences for IL-6 and IFN-gamma. No statistically significant differences were found between clinical forms, although IL-6 and IFN-gamma levels were higher in dengue fever cases than in dengue hemorrhagic fever cases. On the other hand, TNF-alpha levels were higher in dengue hemorrhagic fever than in dengue fever. The levels of IL-6 and TNF-alpha were higher in secondary infection than in primary infection, although IFN-gamma levels were higher in primary infection. These results suggest that IL-6, TNF-alpha and IFN-gamma are involved in dengue infection independently of the clinical form.Este estudo comparou os níveis séricos de IL-6, TNF-alfa e IFN-gama, em crianças menores de um ano com e sem dengue. Os soros foram coletados de um total de 41 crianças residentes no Departamento de Antioquia, Colômbia (27 pacientes com dengue e 14 controles. Os resultados mostraram níveis de citoquinas mais elevadas em crianças com dengue do que naquelas sem dengue, com diferenças estatisticamente significativas para IL-6 and IFN-gama. Não houve diferenças estatisticamente significativas entre formas clínicas, embora os níveis de IL-6 e IFN-gama estivessem mais elevados nos casos de febre do dengue que nos casos de febre hemorrágica do dengue. Por outro lado, os níveis de TNF-alfa estavam mais elevados na febre hemorrágica do dengue que na febre do dengue. Os níveis de IL-6 and TNF-alfa estavam mais elevados em infecções secundárias que em infecções primarias, embora os níveis de IFN-gama estivessem mais elevados em infecções primárias. Estes resultados sugerem que IL-6, TNF-alfa e IFN-gama estejam envolvidos na infecção do dengue, independentemente da forma clínica.

  9. Oral L-arginine modulates blood lactate and interleukin-6 after exercise in HIV-infected men.

    Science.gov (United States)

    Alves, G N; Tavares, A M V; Vieira, P J C; Sprinz, E; Ribeiro, J P

    2014-04-01

    The acute administration of L-arginine (L-arg), a nitric oxide (NO) precursor, reduces lactate (LAC) concentration after exercise in healthy individuals. Lower concentration of L-arg may enhance the action of some inflammatory cytokines in HIV-1 infected patients. We tested the hypothesis that acute L-arg administration may reduce post-exercise blood LAC and inflammatory cytokines levels in HIV-infected patients. 10 HIV-infected men performed 2 maximal incremental cardiopulmonary exercise tests, separated by one week. 30 min before each test, patients received oral placebo or 20 g of L-arg, in random order. Blood LAC, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured before and up to 60 min after exercise. L-arg administration had no significant effect on exercise performance. Compared to placebo, L-arg administration reduced maximal post-exercise blood LAC from 8.7±0.6 to 6.9±0.4 mmol.L-1 (p<0.05). L-arg administration had no significant effect on TNF-alpha or IL-10 concentrations, but increased post-exercise IL-6 (placebo=19±3pg.mL-1; L-arg=63±8 pg.mL-1; p<0.05). In HIV-1 infected men, acute administration of L-arg reduces post-exercise blood LAC and increases IL-6 levels, suggesting the activation of the L-arg-NO pathway, with possible anti-inflammatory consequences. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Expressão local do fator de necrose tumoral alfa na ruptura prematura de membranas Local expression of tumor necrosis factor-alpha on premature rupture of membranes

    Directory of Open Access Journals (Sweden)

    Valquíria Roveran

    2009-05-01

    Full Text Available OBJETIVO: comparar a expressão do fator de necrose tumoral alfa (TNF-α em membranas ovulares com ruptura prematura (RPM e com ruptura oportuna das mesmas; verificar a associação entre a expressão do TNF-α em membranas ovulares e o grau de corioamnionite das mesmas e correlacionar a expressão do TNF-α e o tempo de ruptura das membranas. MÉTODOS: foram analisadas as membranas ovulares de 31 parturientes com RPM, com idade gestacional acima de 34 semanas, e de 14 parturientes com ruptura oportuna das membranas, com idade gestacional igual ou maior de 37 semanas. A detecção da corioamnionite foi feita por meio de estudo histopatológico. A avaliação da expressão do TNF-α foi feita por meio de técnica imunoistoquímica, na qual foi empregado o método streptavidina-biotina-peroxidase (LSAB. RESULTADOS: o tempo médio de ruptura foi de 16,6 horas. A frequência da expressão de TNF-α, nos Grupos Controle e Estudo, não mostrou diferença significante (χ2=6,6; p=0,08. No Grupo Estudo, houve correlação entre o grau de corioamnionite e a intensidade da expressão de TNF-α (coeficiente de Spearman (Rs=0,4; p=0,02. CONCLUSÕES: não houve diferença significante entre as expressões do TNF-α em membranas ovulares com ruptura prematura e com ruptura oportuna das mesmas; no Grupo Estudo, constatou-se associação significante entre a expressão do TNF-α e o grau de corioamnionite e não houve associação entre o tempo de ruptura e a intensidade da expressão do TNF-α.PURPOSE: to compare the expression of tumor necrosis factor-alpha (TNF-α in ovular membranes with premature rupture (MPR and with opportune rupture; to verify the association between the expression of the TNF-α in ovular membranes and the degree of chorioamnionitis, correlating the expression of the TNF-α and the membranes' time of rupture. METHODS: ovular membranes from 31 parturients with MPR, with gestational ages over 34 weeks, and from parturients with opportune

  11. Raised Interleukin 6 Levels: A Risk Factor for Cardiovascular ...

    African Journals Online (AJOL)

    Raised Interleukin 6 Levels: A Risk Factor for Cardiovascular Associated Complications in HIV Positive Zambians before Initiation of Antiretroviral Therapy. P Nhhoma, T Kaile, G Kwenda, M Sinkala, F Mwaba, H. Mantina ...

  12. Retraction RETRACTION of "Tumor necrosis factor alpha gene -308G>A polymorphism association with the risk of esophageal cancer in a Han Chinese population" by H. Zhao, H.W. Zhang, T. Zhang and X.M. Gu - Genet. Mol. Res. 15 (2): gmr.15025866 DOI: http://dx.doi.org/10.4238/gmr.15025866.

    Science.gov (United States)

    Zhao, H; Zhang, H W; Zhang, T; Gu, X M

    2016-10-07

    The retracted article is: Zhao H, Zhang HW, Zhang T and Gu XM (2016). Tumor necrosis factor alpha gene -308G>A polymorphism association with the risk of esophageal cancer in a Han Chinese population. Genet. Mol. Res. 15: gmr.15025866. Two major concerns were found in this article. Firstly, it was found to be substantially equal to the article "Tumor necrosis factor-alpha gene -308G > A polymorphism alters the risk of hepatocellular carcinoma in a Han Chinese population" published in the Diagnostic Pathology Diagnostic Pathology (2014) 9: 199, by Feng et al.; licensee BioMed Central. 2014 - DOI: 10.1186/s13000-014-0199-3. Secondly, the authors do not discuss limitations of their approaches in the discussion. The discussion is largely an elaboration of the literature in the introduction part. However, even in that context, the discussion does not appropriately review the literature and there are frequent references to conclusions that are not supported by the cited literature. The GMR editorial staff was alerted and after a thorough investigation, there is strong reason to believe that the peer review process was failure. Also, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). The authors and their institutions were advised of this serious breach of ethics.

  13. Tumor Necrosis Factor-Alpha and Receptor Activator of Nuclear Factor-κB Ligand Augment Human Macrophage Foam-Cell Destruction of Extracellular Matrix Through Protease-Mediated Processes

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Barascuk, Natasha; Larsen, Lise Korsager

    2012-01-01

    , a major component of extracellular matrix (ECM) in plaques, and to establish whether the pro-inflammatory molecules, tumor necrosis factor (TNF)-alpha, and receptor activator of nuclear factor-κB ligand (RANK-L) increase this degradation. CD14+ monocytes isolated from peripheral blood were differentiated...

  14. In vitro inhibition of enterobacteria-reactive CD4+Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Mangano, K.; Sardesai, N.; D'Alcamo, M.

    2008-01-01

    VGX-1027 is an isozaxoline compound that has recently been found to primarily target the function of murine macrophages but not of T cells, inhibiting secretion of tumor necrosis factor (TNF)-alpha in response to different Toll-like receptor agonists in vitro and in vivo. The well-defined role of...

  15. Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Biggar, R.J.; Johansen, J.S.; Smedby, K.E.

    2008-01-01

    PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...

  16. Interleukin-6, a new target for therapy in multiple myeloma?

    NARCIS (Netherlands)

    van Oers, M. H.; van Zaanen, H. C.; Lokhorst, H. M.

    1993-01-01

    During the past few years much insight has been gained into the immunobiology of multiple myeloma. It has become evident that the growth of myeloma cells is regulated by cytokines, notably interleukin-6. In this paper a brief review is given of the evidence derived from in vitro as well as in vivo

  17. Serotonin Transporter Gene, Depressive Symptoms, and Interleukin-6

    NARCIS (Netherlands)

    Su, Shaoyong; Zhao, Jinying; Bremner, J. Douglas; Miller, Andrew H.; Tang, Weining; Bouzyk, Mark; Snieder, Harold; Novik, Olga; Afzal, Nadeem; Goldberg, Jack; Vaccarino, Viola

    2009-01-01

    Background-We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels. Methods and Results-We genotyped 20 polymorphisms in 360 male twins (mean

  18. Metabolites associated with circulating interleukin-6 in older adults

    Science.gov (United States)

    Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in ...

  19. Interleukin-6 receptor pathways in coronary heart disease

    DEFF Research Database (Denmark)

    Sarwar, Nadeem; Butterworth, Adam S; Freitag, Daniel F

    2012-01-01

    Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied...

  20. Interleukin 6, interleukin 1β, estradiol and testosterone ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... Key words: Oocyte maturation, follicular fluid, interleukin 6, interleukin 1β, testosterone, estradiol. INTRODUCTION. A complex of hormones, growth factors and cytokines regulates the ovarian function. The interaction between immune and endocrine systems is triggered by the action of immune cells within ...

  1. Analysis of interleukin-6 in endotoxin-induced uveitis

    NARCIS (Netherlands)

    Hoekzema, R.; Murray, P. I.; van Haren, M. A.; Helle, M.; Kijlstra, A.

    1991-01-01

    The mechanisms underlying the induction of intraocular inflammation in the rat model of endotoxin-induced uveitis (EIU) and the subsequent development of tolerance after repeated endotoxin injections are poorly understood. Interleukin-6 (IL-6) was measured in the aqueous humor and serum of Lewis

  2. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...... suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis....

  3. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower l...... suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis....

  4. Infections and treatment of patients with rheumatic diseasesTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Atzeni, F.; Bendtzen, K.; Bobbio-Pallavicini, F.

    2008-01-01

    , and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major co-morbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role....../inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night...

  5. [POEMS syndrome: role and value of interleukin-6].

    Science.gov (United States)

    Andrès, E; Courouau, F; Kaltenbach, G; Maloisel, F; Imler, M

    1996-01-01

    POEMS syndrome is a systemic disorder with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The association of POEMS syndrome with lympho-proliferative disorder is very commun. The pathogenesis remains poorly understood but implication of cytokines (interleukins 1 and 6) is suspected. We report a case of a classic POEMS syndrome (with polyneuropathy, hepatomegaly, diabetes melitus, hyperpigmentation, monoclonal IgG lambda, anasarca and solitary plasmocytoma), associated with high serum levels of interleukin 6.

  6. CD4+ T cells of schistosomiasis naturally resistant individuals living in an endemic area produce interferon-gamma and tumour necrosis factor-alpha in response to the recombinant 14KDA Schistosoma mansoni fatty acid-binding protein.

    Science.gov (United States)

    Brito, C F; Caldas, I R; Coura Filho, P; Correa-Oliveira, R; Oliveira, S C

    2000-06-01

    Cellular immune responses to recombinant (r) Sm14 were examined in chronic, treated patients and uninfected individuals living in an endemic area for schistosomiasis. The lymphocyte proliferative responses and cytokine profile to this antigen were evaluated. Peripheral blood mononuclear cells (PBMC) of all groups studied proliferated to rSm14. However, the highest proliferation index to rSm14 was detected in uninfected endemic normal (EN) individuals who are naturally resistant to schistosomiasis. Regarding the cytokines produced, the levels of interleukin (IL)-5 and IL-10, known as Th2 cytokines, were not statistically different among all groups studied. In contrast, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were produced in significantly higher amounts by PBMC of EN individuals following rSm14 stimulation. Additionally, we have determined by flow cytometry that CD4+ T cells from these individuals are the main lymphocyte subpopulation producing IFN-gamma and TNF-alpha. Moreover, we have used rIL-10 or rIFN-gamma, or monoclonal antibodies (MoAb) against these two cytokines to determine their role on cellular reactivity to rSm14. Exogenous IL-10 suppressed T-cell proliferation and neutralization of endogenous IL-10 restored lymphocyte activation and enhanced IFN-gamma and TNF-alpha production in chronically infected patients. In contrast, the addition of anti-IFN-gamma totally abrogated the PBMC proliferation within the EN group. This study demonstrated that IL-10 is an important cytokine down-regulating T-cell responses in chronic schistosomiasis, whereas lymphocyte proliferation in the uninfected resistant group is dependent on IFN-gamma. Taken together these results suggest that Th1 type of immune response induced in EN individuals to a specific schistosome antigen might be associated with resistance to infection and also highlighted the importance of Sm14 as a potential vaccine candidate.

  7. Associations of tumor necrosis factor alpha receptor type 1 with kidney function decline, cardiovascular events, and mortality risk in persons with coronary artery disease: Data from the Heart and Soul Study.

    Science.gov (United States)

    Park, Meyeon; Maristany, Daniela; Huang, Debbie; Shlipak, Michael G; Whooley, Mary

    2017-08-01

    Tumor necrosis factor receptor type 1 (TNFR1) is associated with kidney disease and mortality risk in various populations. Whether or not kidney function mediates mortality risk is unknown. We evaluated associations of TNFR1 levels with measures of kidney function, cardiovascular events, and mortality in a population of veterans with stable ischemic heart disease. TNFR1 was measured from baseline serum samples in the Heart and Soul Study; elevated levels were defined by the highest quartile (Q4, >3.4 ng/ml). We evaluated associations of high TNFR1 with baseline estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) and with longitudinal changes in eGFR (rapid loss), as well as with incident myocardial infarction (MI), heart failure hospitalizations (HF), and mortality over a median follow-up time of 8.9 years. Covariates included demographics and comorbid conditions. Among 985 participants who had TNFR1 measurements, median TNFR1 was 2.33 ng/ml (IQR 1.8-3.1). Relative to Q1, Q4 had higher risk of eGFR <60 ml/min/1.73 m 2 (RR 11.71 [95% CI 5.46, 25.11]); ACR ≥ 30 mg/g (2.44 [1.15, 5.19]); and rapid loss in kidney function (2.10 [1.12, 3.92]). Although TNFR1 Q4 was associated with MI, HF, and mortality after demographic adjustment, there were no associations in fully-adjusted models (1.04 [0.44, 2.49]; 1.02 [0.48, 2.15]; 1.42 [0.88, 2.28], respectively). Levels of TNFR1 are associated longitudinally with kidney function decline but not with MI, HF or mortality risk after adjustment. Kidney disease may mediate the risk of MI, HF, and mortality associated with TNFR1. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Tumor necrosis factor-alpha and apoptosis signal-regulating kinase 1 control reactive oxygen species release, mitochondrial autophagy, and c-Jun N-terminal kinase/p38 phosphorylation during necrotizing enterocolitis.

    Science.gov (United States)

    Baregamian, Naira; Song, Jun; Bailey, C Eric; Papaconstantinou, John; Evers, B Mark; Chung, Dai H

    2009-01-01

    Oxidative stress and inflammation may contribute to the disruption of the protective gut barrier through various mechanisms; mitochondrial dysfunction resulting from inflammatory and oxidative injury may potentially be a significant source of apoptosis during necrotizing enterocolitis (NEC). Tumor necrosis factor (TNF)-alpha is thought to generate reactive oxygen species (ROS) and activate the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway. Hence, the focus of our study was to examine the effects of TNF-alpha/ROS on mitochondrial function, ASK1-JNK/p38 cascade activation in intestinal epithelial cells during NEC. We found (a) abundant tissue TNF-alpha and ASK1 expression throughout all layers of the intestine in neonates with NEC, suggesting that TNF-alpha/ASK1 may be a potential source (indicators) of intestinal injury in neonates with NEC; (b) TNF-alpha-induced rapid and transient activation of JNK/p38 apoptotic signaling in all cell lines suggests that this may be an important molecular characteristic of NEC; (c) TNF-alpha-induced rapid and transient ROS production in RIE-1 cells indicates that mitochondria are the predominant source of ROS, demonstrated by significantly attenuated response in mitochondrial DNA-depleted (RIE-1-rho) intestinal epithelial cells; (d) further studies with mitochondria-targeted antioxidant PBN supported our hypothesis that effective mitochondrial ROS trapping is protective against TNF-alpha/ROS-induced intestinal epithelial cell injury; (e) TNF-alpha induces significant mitochondrial dysfunction in intestinal epithelial cells, resulting in increased production of mtROS, drop in mitochondrial membrane potential (MMP) and decreased oxygen consumption; (f) although the significance of mitochondrial autophagy in NEC has not been unequivocally shown, our studies provide a strong preliminary indication that TNF-alpha/ROS-induced mitochondrial autophagy may play a role in NEC, and this process is a

  9. Muscular Interleukin-6 and Its Role as an Energy Sensor

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund

    2012-01-01

    muscle-liver and muscle-fat cross talk. The myokine prototype is interleukin-6 (IL-6). During exercise, contracting skeletal muscles release IL-6. It appears that IL-6 works as an energy sensor and exerts both local and endocrine metabolic effects. Given that skeletal muscle is the largest organ...... in the human body, the discovery of contracting muscle as a cytokine producing organ opens for a whole new paradigm: If the endocrine function of the muscle is not stimulated through contractions, it will cause malfunction of several organs and tissues of the body....

  10. Efficacy of scaling and root planning with and without adjunct Nd:YAG laser therapy on clinical periodontal parameters and gingival crevicular fluid interleukin 1-beta and tumor necrosis factor-alpha levels among patients with periodontal disease: A prospective randomized split-mouth clinical study.

    Science.gov (United States)

    Abduljabbar, Tariq; Vohra, Fahim; Kellesarian, Sergio Varela; Javed, Fawad

    2017-04-01

    Limited evidence exists regarding the role of scaling and root planning (SRP) with adjunct neodymium yttrium aluminum garnet (Nd:YAG) laser therapy in reducing periodontal parameters (plaque index [PI], bleeding on probing [BOP] and probing pocket depth [PPD]) and levels of proinflammatory cytokines in the gingival crevicular fluid (GCF) among patients with periodontal disease (PD). The aim was to assess the effect of SRP with and without adjunct Nd:YAG laser therapy on clinical periodontal parameters and GCF interleukin 1-beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels among patients with PD. Demographic data was collected using a questionnaire. Mandibular right and left quadrants were randomly divided into test- (SRP+Nd:YAG laser) and control-sites (SRP alone). PI, BOP and PPD were assessed and GCF IL-1β and TNF-α levels were measured at baseline and at 3- and 6-month follow-up. Level of significance was set at Pperiodontal inflammatory parameters and GCF IL-1β and TNF-α levels compared with SRP alone. Copyright © 2017. Published by Elsevier B.V.

  11. Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Biggar, R.J.; Johansen, J.S.; Smedby, K.E.

    2008-01-01

    PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...... in nodular sclerosis Hodgkin lymphoma. EXPERIMENTAL DESIGN: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N=470) and population controls from Denmark (n=245 for YKL-40; n=348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed...... by linear regression, adjusting for age and sex. RESULTS: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, PHodgkin lymphoma patients (n=176), levels were correlated...

  12. Implication of Tumor Necrosis Factor - Alpha in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Dan MIHU

    2008-12-01

    Full Text Available Introduction: Preeclampsia is an exacerbation of a generalized inflammatory response, physiologically present in the third trimester of pregnancy.Aim: The aim of the study consists in the evaluation of proinflammatory cytokine TNF-α in the context of preeclampsia. Material and Method: A transversal study was performed in three groups of patients: non-pregnant patients, patients with normal pregnancies in the third trimester, patients with preeclampsia. Serum TNF-α levels were determined using the immunometric sandwich EIA method.Results: The results obtained confirm a significant increase (p<0.01 in circulating TNF-α levels in the last trimester of pregnancy, compared to the non-pregnant status. Significantly increased serum TNF-α concentrations (p<0.001 were also found in pregnant patients with preeclampsia, compared to normotensive pregnant women. Conclusion: This proinflammatory cytokine can be a potential marker of the severity of the preeclamptic syndrome, without being an indicator of the fetal status at birth.

  13. Tumour necrosis factor alpha (TNF-α) genetic polymorphisms and ...

    Indian Academy of Sciences (India)

    Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People's Republic of China; Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi 530021, People's Republic of China ...

  14. Tumour necrosis factor alpha and interleukin 10 gene ...

    Indian Academy of Sciences (India)

    2011-08-19

    Aug 19, 2011 ... Hypertension was defined according to Joint National Committee VI–VII, as a systolic blood pressure >140 mm Hg and/or a diastolic blood pressure. >90 mm Hg based on the average of two blood pressure measurements. Diabetes was diagnosed if fasting plasma glucose was >126 mg/dL, in accordance ...

  15. Tumor necrosis factor-alpha modulates human in vivo lipolysis

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Fischer, Christian P; Ibfelt, Tobias

    2008-01-01

    in lipolysis, increasing circulatory free fatty acid (FFA) levels. SUBJECTS AND METHODS: Using a randomized controlled, crossover design, healthy young male individuals (n = 10) received recombinant human (rh) TNF-alpha (700 ng/m(-2).h(-1)) for 4 h, and energy metabolism was evaluated using a combination...... of tracer dilution methodology and arterial-venous differences over the leg. RESULTS: Plasma TNF-alpha levels increased from 0.7 +/- 0.04 to 16.7 +/- 1.8 pg/ml, and plasma IL-6 increased from 1.0 +/- 0.2 to 9.2 +/- 1.0 pg/ml (P rhTNF-alpha infusion. Here, we demonstrate that 4-h rh......TNF-alpha infusion increases whole body lipolysis by 40% (P rhTNF-alpha infusion. CONCLUSION...

  16. Tumour necrosis factor alpha (TNF-α) genetic polymorphisms and ...

    Indian Academy of Sciences (India)

    Sensitivity analysis of the summary odds ratio coefficients on the association between TNF-α-308G/A polymorphism and AILD risk using a random effects model. (A allele vs G allele). Results were computed by omitting each study in turn. Error bars are 95% confidence interval. Journal of Genetics, Vol. 92, No. 3, December ...

  17. Tumour necrosis factor alpha and interleukin 10 gene ...

    Indian Academy of Sciences (India)

    2011-08-19

    Aug 19, 2011 ... TNF(-308) promoter polymorphism and stroke risk in children with sickle cell anemia. Stroke 38, 2241–2246. Karahan Z. C., Deda G., Sipahi T., Elhan A. H. and Akar N. 2005. TNF-alpha -308G/A and IL-6 -174 G/C polymorphisms in the. Turkish pediatric stroke patients. Thromb. Res. 115, 393–398. Koch W.

  18. Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.

    Science.gov (United States)

    Gillies, Nicola; Pendharkar, Sayali A; Asrani, Varsha M; Mathew, Juby; Windsor, John A; Petrov, Maxim S

    2016-01-01

    Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. Interleukin-6 appears to be implicated in the development of chronic

  19. Interleukin-6 mediates host defense responses induced by abdominal surgery

    NARCIS (Netherlands)

    Wortel, C. H.; van Deventer, S. J.; Aarden, L. A.; Lygidakis, N. J.; Büller, H. R.; Hoek, F. J.; Horikx, J.; ten Cate, J. W.

    1993-01-01

    Cytokines have been implicated as pivotal mediators of the host defense reaction. In patients undergoing surgery we investigated the relationship between such mediators and postoperative host defense responses. Tumor necrosis factor (TNF) was determined with an immunoradiometric assay, interleukin

  20. Quantification of active infliximab in human serum with liquid chromatography-tandem mass spectrometry using a tumor necrosis factor alpha -based pre-analytical sample purification and a stable isotopic labeled infliximab bio-similar as internal standard: A target-based, sensitive and cost-effective method.

    Science.gov (United States)

    El Amrani, Mohsin; van den Broek, Marcel P H; Göbel, Camiel; van Maarseveen, Erik M

    2016-07-08

    The therapeutic monoclonal antibody Infliximab (IFX) is a widely used drug for the treatment of several inflammatory autoimmune diseases. However, approximately 10% of patients develop anti-infliximab antibodies (ATIs) rendering the treatment ineffective. Early detection of underexposure to unbound IFX would result in a timely switch of therapy which could aid in the treatment of this disease. Streptavidin coated 96 well plates were used to capture biotinylated-tumor necrosis factor -alpha (b-TNF-α), which in turn was used to selectively extract the active form of IFX in human serum. After elution, IFX was digested using trypsin and one signature peptide was selected for subsequent analysis on liquid chromatography-tandem mass spectrometry (LC-MS/MS). The internal standard used was a stable isotopic labeled IFX bio-similar. The assay was successfully validated according to European Medicines Agency (EMA) guidelines and was found to be linear in a range of 0.5-20μg/mL (r(2)=0.994). Lower limit of quantification for the assay (<20% CV) was 0.5μg/mL, requiring only 2μL of sample. Cross-validation against enzyme-linked immunosorbent assay (ELISA) resulted in a high correlation between methods (r(2)=0.95 with a ρc=0.83) and the accuracy was in line with previously published results. In conclusion, a sensitive, robust and cost-effective method was developed for the bio-analysis of IFX with LC-MS/MS by means of a target-based pre-analytical sample purification. Moreover, low volume and costs of consumables per sample promote its feasibility in (pre)clinical studies and in therapeutic drug monitoring. This method should be considered as first choice due to its accuracy and multiple degree of selectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Aptamer conjugated silver nanoparticles for the detection of interleukin 6

    Science.gov (United States)

    Locke, Andrea K.; Norwood, Nicole; Marks, Haley L.; Schechinger, Monika; Jackson, George W.; Graham, Duncan; Coté, Gerard L.

    2016-03-01

    The controlled assembly of plasmonic nanoparticles by a molecular binding event has emerged as a simple yet sensitive methodology for protein detection. Metallic nanoparticles (NPs) coated with functionalized aptamers can be utilized as biosensors by monitoring changes in particle optical properties, such as the LSPR shift and enhancement of the SERS spectra, in the presence of a target protein. Herein we test this method using two modified aptamers selected for the protein biomarker interleukin 6, an indicator of the dengue fever virus and other diseases including certain types of cancers, diabetes, and even arthritis. IL6 works by inducing an immunological response within the body that can be either anti-inflammatory or pro-inflammatory. The results show that the average hydrodynamic diameter of the NPs as measured by Dynamic Light Scattering was ~42 nm. After conjugation of the aptamers, the peak absorbance of the AgNPs shifted from 404 to 408 nm indicating a surface modification of the NPs due to the presence of the aptamer. Lastly, preliminary results were obtained showing an increase in SERS intensity occurs when the IL-6 protein was introduced to the conjugate solution but the assay will still need to be optimized in order for it to be able to monitor varying concentration changes within and across the desired range.

  2. Salivary Interleukine 6 and its role on developing periodentitis

    Directory of Open Access Journals (Sweden)

    Thana Mohammed Juda

    2016-03-01

    Full Text Available Back ground Interleukin-6 (IL-6 is biologically active small protein molecules known as cytokines .These cytokines are produced by leukocytes, adipocytes, and endothelial cells, and it is involved mainly in inflammatory processes. IL-6 has a role in stimulating the immune response as trigger to infection or trauma through the production of acute-phase proteins that accompany the inflammatory process. IL-6 synthesized according to code from messenger RNA, so their production in tissue in responce of inflammation are increased by the action of increasing expression of its own specific messenger RNA and the expression levels of the mRNAs were either up- or down-regulated by adjacent focal infiltrating lymphoid cells according to the state of periodontal in health and disease so the local concentration of cytokines reflect the state of inflammatory process under control at nuclear level. The aim of study is to evaluate the inflammatory cytokine that associated the process of periodentitis Methods: Salivary specimens were obtained from patients having chronic periodentitis and healthy subject act as control group. The assessment of IL6 concentrations were established by technique enzyme linked immunoassay. . Results: level of IL-6 in saliva sample after evaluation the result showed statistically significant difference between patients and control . Conclusions: The result obtained from this study revealed that estimated salivary IL 6 can be used in management protocol of process of periodentitis

  3. Interleukin-6 blockade Improves Autonomic Dysfunction in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ashit Syngle

    2015-01-01

    Full Text Available Autonomic nervous system (ANS involvement in rheumatoid arthritis (RA is well recognised and contributes to arrhythmia and sudden death. However, there is no study documented the therapeutic efficacy on autonomic neuropathy (AN in RA. This is the first reported observation of improvement in AN with interleukin-6 (IL-6 blockade with tocilizumab in RA. We report a case of 61-year old female with seropositive RA with severe disease activity, investigated for autonomic neuropathy. A battery of non invasive tests was used for accurate assessment of AN function based on assessment of peripheral sympathetic autonomic function and cardiovascular reflex tests. Tocilizumab 8mg/kg intravenous infusion at weeks 0, 4 and 8 was added to her treatment regimen. Cardiovascular autonomic function tests at baseline showed marked abnormalities of parasympathetic cardiovascular reflexes. After the first dose of tocilizumab there was a rapid improvement with normalization of parasympathetic autonomic activity with subsequent doses. IL-6 blockade with tocilizumab seems to have the potential to improve the vagus nerve mediated parasympathetic neuropathy and hence has the potential to restore cholinergic anti-inflammatory pathway.

  4. Interleukin-6 in Schizophrenia-Is There a Therapeutic Relevance?

    Science.gov (United States)

    Borovcanin, Milica Milovan; Jovanovic, Ivan; Radosavljevic, Gordana; Pantic, Jelena; Minic Janicijevic, Slavica; Arsenijevic, Nebojsa; Lukic, Miodrag L

    2017-01-01

    Renewing interest in immune aspects of schizophrenia and new findings about the brain-fat axis encourage us to discuss the possible role of interleukin-6 (IL-6) in schizophrenia. Previously, it was suggested that a primary alteration of the innate immune system may be relevant in schizophrenia. Functional dichotomy of IL-6 suggests that this chemical messenger may be responsible for regulating the balance between pro- and anti-inflammatory responses, with tissue-specific properties at the periphery and in the central nervous system. Specific phase of this chronic and deteriorating disorder must be considered, which can involve IL-6 in acute or possible chronic inflammation and/or autoimmunity. We give an overview of IL-6 role in the onset and progression of this disorder, also considering cognitive impairment and metabolic changes in patients with schizophrenia. Data suggest that decreased serum level of IL-6 following antipsychotic therapy could be predisposing factor for the development of obesity and obesity-related metabolic disorders in schizophrenia. As we reviewed, the IL-6 plays significant role in disease genesis and progression, so the use of specific inhibitors may not only be beneficial for exacerbation and alleviation of positive symptoms, but may attenuate cognitive impairment in patients with schizophrenia.

  5. Interleukin-6 in Schizophrenia—Is There a Therapeutic Relevance?

    Science.gov (United States)

    Borovcanin, Milica Milovan; Jovanovic, Ivan; Radosavljevic, Gordana; Pantic, Jelena; Minic Janicijevic, Slavica; Arsenijevic, Nebojsa; Lukic, Miodrag L.

    2017-01-01

    Renewing interest in immune aspects of schizophrenia and new findings about the brain-fat axis encourage us to discuss the possible role of interleukin-6 (IL-6) in schizophrenia. Previously, it was suggested that a primary alteration of the innate immune system may be relevant in schizophrenia. Functional dichotomy of IL-6 suggests that this chemical messenger may be responsible for regulating the balance between pro- and anti-inflammatory responses, with tissue-specific properties at the periphery and in the central nervous system. Specific phase of this chronic and deteriorating disorder must be considered, which can involve IL-6 in acute or possible chronic inflammation and/or autoimmunity. We give an overview of IL-6 role in the onset and progression of this disorder, also considering cognitive impairment and metabolic changes in patients with schizophrenia. Data suggest that decreased serum level of IL-6 following antipsychotic therapy could be predisposing factor for the development of obesity and obesity-related metabolic disorders in schizophrenia. As we reviewed, the IL-6 plays significant role in disease genesis and progression, so the use of specific inhibitors may not only be beneficial for exacerbation and alleviation of positive symptoms, but may attenuate cognitive impairment in patients with schizophrenia. PMID:29163240

  6. Diesel exhaust particles induced release of interleukin 6 and 8 by (primed) human bronchial epithelial cells (BEAS 2B) in vitro.

    Science.gov (United States)

    Steerenberg, P A; Zonnenberg, J A; Dormans, J A; Joon, P N; Wouters, I M; van Bree, L; Scheepers, P T; Van Loveren, H

    1998-01-01

    Several epidemiological studies have recently shown associations of increased premature mortality rates with ambient particulate air pollution. Diesel exhaust particles (DEP) may constitute an important part of (ultra)fine particulate air pollution in urban areas and may therefore contribute to its toxicity. Epithelial lining of the respiratory tract may be the first target of the toxic effects of DEP, that upon exposure may release pro-inflammatory mediators such as interleukin 6 and 8 (IL-6, IL-8), ultimately causing airway tissue damage and immune alterations. In this study the effects of in vitro DEP exposure (0.04-0.33 mg/mL) on IL-6, IL-8 production by a human bronchial epithelial cell line (BEAS-2B) were investigated. For comparison, the production of interleukins during exposure to silica and titanium oxide (TiO2) were also studied, representing relatively toxic and non-toxic particles, respectively. Scanning and transmission electron microscopy showed that the size of the DEP particles ranged between 25 to 35 nm and that DEP was phagocytized by BEAS-2B cells. An increase in IL-6 and IL-8 production (11- and 4-fold, respectively) was found after 24 or 48 h of exposure to DEP compared to the non-exposed cells. This increase was lower compared to silica (17- and 3.3-fold) and higher as compared to TiO2 which showed no increase for IL-6 and IL-8. To study the DEP effect on inflammation-primed cells, BEAS-2B cells were exposed to both tumor necrosis factor-alpha (TNF-alpha) and subsequently to DEP. Exposure to TNF-alpha caused a strong increase in IL-6 and IL-8 production. Additive effects on the IL-6 and IL-8 production by BEAS-2B cells were found after TNF-alpha priming and subsequently exposure to DEP, only at a low dose of DEP and TNF-alpha (0.05-0.2 ng/mL). In conclusion, BEAS-2B phagocytized DEP and produced an increased amount of IL-6 and IL-8. In TNF-alpha primed BEAS-2B cells, DEP increased interleukin production only at low concentrations of DEP and

  7. Interleukin-6 genotypes and serum levels in Chinese Hui population.

    Science.gov (United States)

    Gao, Shu-Ping; Liang, Shu; Pan, Min; Sun, Rong-Liang; Chen, Chu; Luan, Hong; Jiang, Min-Hui

    2014-01-01

    Interleukin-6 (IL-6) is a key pro-inflammatory cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals. The Chinese Hui is one of the largest ethnic minorities, little is known about the distribution of IL-6 genetic variations and their effects on serum levels in Hui population. The aim of the present study is to determine the prevalence of -174G/C (rs1800795), -597G/A (rs1800797), and -634C/G (rs1800796) polymorphisms in the IL-6 gene promoter region and their association with IL-6 serum levels in the Ningxia Hui population. A total of 96 Hui subjects, (57 men and 39 women; mean age 49.65 ± 19.73 years) unrelated nationality residents in Ningxia Hui Autonomous Region were enrolled. Genotyping of the three polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis and then confirmed by direct sequencing. The -174G/C (97.92% GG, 2.08% GC, and 0% CC) and -597G/A (98.96% GG, 1.04% GA, and 0% AA) polymorphisms were rare. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 54.17%, 40.62%, and 5.21%, respectively in total studied subjects, the derived allele frequencies for the C and G alleles were 74.48% and 25.52%. Increased IL-6 levels were correlated with the IL-6 -634G allele carriers (CG+GG genotypes). The results suggest that IL-6 -174G/C and -597G/A are rare but -634C/G is common in the Ningxia Hui population, and the -634G allele is associated with circulating levels of IL-6.

  8. Retinol as a micronutrients related to cervical local immunity: The expression of tumor necrosis factor-alpha specifically stimulated with E6 epitope of human papillomavirus type-16 and ratio of CD4+/CD8+ T cell in natural history of cervical cancer

    Science.gov (United States)

    Utami, T. W.; Aziz, M. F.; Ibrahim, F.; Andrijono

    2017-08-01

    Retinol is one of the antioxidant micronutrients that plays essential roles in the immune system, by preventing the persistence of modulating CD4+ and CD8+ T cells and cytokines production. Tumor Necrosis Factor-Alpha (TNF-α) is an acute pro-inflammatory cytokine which has many crucial roles in controlling HPV. In contrast, when persistent infection occurs, TNF-α induces carcinogenesis. The ratio of CD4+ cells to CD8+ T cells and adequate TNF-α production in acute HPV infection are key points for clearance. The aim of this research is to analyze the sufficiency level of retinol deposit, the expression of TNF-α, and the ratio of CD4+: CD8+ T cells in a normal cervix, clearance and persistent HPV subclinical infection, and cervical cancer group. The sufficiency level of retinol deposit was analyzed from peripheral blood using the ELISA method. The cervico-vaginal secretions, which were incubated for 24 hours, were stimulated specifically by E6 epitope HPV type-16, measuring TNF-α expression semi-quantitatively by the ELISpot method and CD4+/CD8+ T cells quantitatively by flowcytometry method. The sufficient level of retinol deposit in a normal cervix, clearance HPV subclinical infection, persistent, and cervical cancer group was 85%, 75% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89), respectively. The expression of TNF-α in normal cervix group was 10%, while for cervical cancer it was 75% (OR 27.00; p < 0.001). There was no expression in clearance and persistent HPV subclinical infection groups. A high ratio of CD4+: CD8+ T cells in the normal cervix and cervical cancer group was 10% and 25% (OR 0.33). There was no high ratio of CD4+: CD8+ T cells in clearance (OR 1.22) and persistent (OR 0.95) HPV subclinical infection groups. This study was able to prove that the normal cervix group has the highest retinol deposit sufficiency level and the cervical cancer group has the highest TNF-α expression (OR 27; p < 0.001). The lowest of retinol deposit sufficiency

  9. Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis.

    Science.gov (United States)

    Tournadre, Anne; Pereira, Bruno; Dutheil, Fréderic; Giraud, Charlotte; Courteix, Daniel; Sapin, Vincent; Frayssac, Thomas; Mathieu, Sylvain; Malochet-Guinamand, Sandrine; Soubrier, Martin

    2017-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality associated with cardiometabolic disorders including dyslipidaemia, insulin resistance, and cachectic obesity. Tumour necrosis factor inhibitors and interleukin 6 receptor blocker licensed for the treatment of RA decrease inflammation and could thus improve cardiovascular risk, but their effects on body composition and metabolic profile need to be clarified. We investigated the effects of tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, on body composition and metabolic profile in patients treated for RA. Twenty-one active RA patients treated with TCZ were included in a 1 year open follow-up study. Waist circumference, body mass index, blood pressure, lipid profile, fasting glucose, insulin, serum levels of adipokines and pancreatic/gastrointestinal hormones, and body composition (dual-energy X-ray absorptiometry) were measured at baseline and 6 and 12 months of treatment. At baseline, RA patients were compared with 21 non-RA controls matched for age, sex, body mass index, and metabolic syndrome. Compared with controls, body composition was altered in RA with a decrease in total and appendicular lean mass, whereas fat composition was not modified. Among RA patients, 28.6% had a skeletal muscle mass index below the cut-off point for sarcopaenia (4.8% of controls). After 1 year of treatment with TCZ, there was a significant weight gain without changes for fat mass. In contrast, an increase in lean mass was observed with a significant gain in appendicular lean mass and skeletal muscle mass index between 6 and 12 months. Distribution of the fat was modified with a decrease in trunk/peripheral fat ratio and an increase in subcutaneous adipose tissue. No changes for waist circumference, blood pressure, fasting glucose, and atherogenic index were observed. Despite weight gain during treatment with TCZ, no increase in fat but a modification in fat

  10. The membrane-type estrogen receptor G-protein-coupled estrogen receptor suppresses lipopolysaccharide-induced interleukin 6 via inhibition of nuclear factor-kappa B pathway in murine macrophage cells.

    Science.gov (United States)

    Okamoto, Mariko; Suzuki, Takuto; Mizukami, Yoichi; Ikeda, Teruo

    2017-11-01

    The female sex hormone estrogen exerts anti-inflammatory effects. The G-protein-coupled estrogen receptor (GPER) has been recently identified as a novel membrane-type estrogen receptor that can mediate non-genomic estrogenic effects on many cell types. We previously demonstrated that GPER inhibits tumor necrosis factor alpha-induced expression of interleukin 6 (IL-6) through repression of nuclear factor-kappa B (NF-κB) promoter activity using human breast cancer cells. Although several reports have indicated that GPER suppresses Toll-like receptor-induced inflammatory cytokine expression in macrophages, the molecular mechanisms of the inhibition of cytokine production via GPER remain poorly understood. In the present study, we examined GPER-mediated inhibition of IL-6 expression induced by lipopolysaccharide (LPS) stimulation in a mouse macrophage cell line. We found that the GPER agonist G-1 inhibited LPS-induced IL-6 expression in macrophage cells, and this inhibition was due to the repression of NF-κB promoter activity by GPER. G-1 treatment also decreased the phosphorylation of inhibitor of κB kinases. Among the mitogen-activated protein kinases, the phosphorylation of c-jun N-terminal kinase (JNK) was increased by G-1. These findings delineate the novel mechanism of the inhibition of LPS-induced IL-6 through GPER-activated JNK-mediated negative regulation of the NF-κB pathway in murine macrophage cells, which links anti-inflammatory effects to estrogen. © 2017 Japanese Society of Animal Science.

  11. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    T. Robak

    1998-01-01

    Full Text Available We investigated the serum concentrations of interleukin-6 (IL-6 and two IL-6 family of cytokines (leukaemia inhibitory factor (LIF and ciliary neurotrophic factor (CNTF as well as IL-6 soluble receptor (sIL-6R using an enzyme-linked immunosorbent assay (ELISA in 66 patients with rheumatoid arthritis (RA and 24 healthy controls. We examined a possible association between the serum levels of these peptides and RA activity according to the Mallya and Mace scoring system and Ritchie's index. We also evaluated the correlation between the serum levels of IL-6, LIF, CNTF and sIL-6R and duration of the disease and calculated sIL-6R/IL-6 ratio in RA patients and in the control group. IL-6 and sIL-6R were detectable in all 66 patients with RA and 24 normal individuals. LIF was also found in the serum of all patients with RA and in 16 (66.7% normal individuals. In contrast CNTF was measurable only in 15 (22.7% patients with RA and 24 (33.3% normal individuals. The highest IL-6 and sIL-6R levels were found in the patients with Stages 3 and 4 of RA activity and the lowest in the control group. In contrast there were no statistically significant diferences between the LIF and CNTF levels in RA patients and normal individuals. We found positive correlation between IL-6 and sIL-6R concentrations and Ritchie's index and a lack of such correlation with LIF and CNTF. IL-6 serum level correlated positively with the disease duration, but sIL-6R, LIF and CNTF did not. Serum sIL-6R/IL-6 ratio was significantly lower in RA patients than in healthy controls. In conclusion, an increase in the serum levels of IL-6 and sIL-6R, but not LIF and CNTF concentrations, may be useful markers for RA activity.

  12. Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion

    DEFF Research Database (Denmark)

    Carey, A.; Wolsk, Emil; Bruce, C.

    2006-01-01

    protein 1 (UCP1) gene was detected in the adipose tissue of some of the diabetic patients, but not in the control subjects. The following genes were increased by infusion of recombinant human IL6 in both groups: SOCS1/3, resistin, adiponectin, AMP-activated protein kinase-alpha-1 and PPARA. Plasma tumour...... necrosis factor alpha, adiponectin and resistin were all unaffected by IL6 infusion, but plasma resistin was lower in the diabetic subjects than in control subjects. Conclusions/interpretation  The observation that PPARGC1A and the PPARs were upregulated in the adipose tissue of type 2 diabetic patients...

  13. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.

    Science.gov (United States)

    McCormick, C; Freshney, R I; Speirs, V

    1995-02-01

    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.

  14. Motorcycle exhaust induces reproductive toxicity and testicular interleukin-6 in male rats.

    Science.gov (United States)

    Huang, Jing-Ying; Liao, Jiunn-Wang; Liu, Yi-Chun; Lu, Shui-Yuan; Chou, Chen-Ping; Chan, Wei-Hung; Chen, Shee-Uan; Ueng, Tzuu-Huei

    2008-05-01

    Motorcycle exhaust (ME) from two-stroke engines contains many toxicants and poses a potential health hazard. The major objectives of the present study were to investigate the male reproductive toxicity of ME and the underlying mechanisms of toxicity. Male Wistar rats were exposed to ME by inhalation 1 h each in the morning and afternoon, Monday through Friday. Exposures to 1:50 diluted ME for 4 weeks or to 1:10 diluted ME for 2 and 4 weeks showed concentration- and time-dependent decreases of testicular weight, spermatid number, and cauda epididymal sperm number. Subsequent studies were done using 4-week exposure to 1:10 diluted ME. ME caused histopathological changes including testicular spermatocytic necrosis and seminiferous tubule atrophy and cauda epididymal formation of clusters of pyknotic and necrotic sperm cells. ME-exposed male rats mated with untreated females showed decreases of male mating index and female fertility index and an increase of implantation site loss. ME decreased 7-ethoxycoumarin O-deethylase and superoxide dismutase activities but induced proinflammatory cytokine interleukin-6 (IL-6) messenger RNA (mRNA) in the testis. Male rats were exposed to ME with or without cotreatment with 50 mg/kg vitamin E orally for 4 weeks. ME decreased serum testosterone concentration. This effect was reversed by cotreatment with vitamin E. ME decreased testicular spermatid number and induced IL-6 mRNA and protein. These effects were also reversed by the vitamin E cotreatment. The present findings show that ME causes male reproductive effects and induces testicular IL-6 in rats by mechanisms involving induction of oxidative stress and inhibition of steroidogenesis.

  15. Inhibition of interleukin-6 expression by the V protein of parainfluenza virus 5

    International Nuclear Information System (INIS)

    Lin Yuan; Sun Minghao; Fuentes, Sandra M.; Keim, Celia D.; Rothermel, Terri; He Biao

    2007-01-01

    The V protein of parainfluenza virus 5 (PIV5) plays an important role in the evasion of host immune responses. The V protein blocks interferon (IFN) signaling in human cells by causing degradation of the STAT1 protein, a key component of IFN signaling, and blocks IFN-β production by preventing nuclear translocation of IRF3, a key transcription factor for activating IFN-β promoter. Interleukin-6 (IL-6), along with tumor necrosis factor (TNF)-α and IL-1β, is a major proinflammatory cytokine that plays important roles in clearing virus infection through inflammatory responses. Many viruses have developed strategies to block IL-6 expression. Wild-type PIV5 infection induces little, if any, expression of cytokines such as IL-6 or TNF-α, whereas infection by a mutant PIV5 lacking the conserved C-terminal cysteine rich domain (rPIV5VΔC) induced high levels of IL-6 expression. Examination of mRNA levels of IL-6 indicated that the transcription activation of IL-6 played an important role in the increased IL-6 expression. Co-infection with wild-type PIV5 prevented the activation of IL-6 transcription by rPIV5VΔC, and a plasmid encoding the full-length PIV5 V protein prevented the activation of IL-6 promoter-driven reporter gene expression by rPIV5VΔC, indicating that the V protein played a role in inhibiting IL-6 transcription. The activation of IL-6 was independent of IFN-β even though rPIV5VΔC-infected cells produced IFN-β. Using reporter gene assays and chromatin immunoprecipitation (ChIP), it was found that NF-κB played an important role in activating expression of IL-6. We have proposed a model of activating and inhibiting IL-6 transcription by PIV5

  16. Interleukin-6 but not soluble adhesion molecules has short-term ...

    African Journals Online (AJOL)

    Interleukin-6 but not soluble adhesion molecules has short-term prognostic value on mortality in patients with acute ST-segment elevation myocardial infarction. ZX Fan, Q Hua, J Tan, J Gao, RK Liu, Z Yang ...

  17. Serum Interleukin-6 in Patients with Burning Mouth Syndrome and Relationship with Depression and Perceived Pain

    Directory of Open Access Journals (Sweden)

    Qianming Chen

    2007-01-01

    Conclusions. Serum interleukin-6 in patients with burning mouth syndrome is decreased and negatively correlated to chronic pain. Both psychological and neuropathic disorders might act as precipitating factors in BMS etiopathogenesis.

  18. Clinical effectiveness and cost-effectiveness of use of therapeutic monitoring of tumour necrosis factor alpha (TNF-α) inhibitors [LISA-TRACKER® enzyme-linked immunosorbent assay (ELISA) kits, TNF-α-Blocker ELISA kits and Promonitor® ELISA kits] versus standard care in patients with Crohn's disease: systematic reviews and economic modelling.

    Science.gov (United States)

    Freeman, Karoline; Connock, Martin; Auguste, Peter; Taylor-Phillips, Sian; Mistry, Hema; Shyangdan, Deepson; Court, Rachel; Arasaradnam, Ramesh; Sutcliffe, Paul; Clarke, Aileen

    2016-11-01

    Systematic reviews and economic modelling of clinical effectiveness and cost-effectiveness of therapeutic monitoring of tumour necrosis factor alpha (TNF-α) inhibitors [using LISA-TRACKER ® enzyme-linked immunosorbent assay (ELISA) kits (Theradiag, Marne La Vallee, France, or Alpha Laboratories, Heriot, UK), TNF-α-Blocker ELISA kits (Immundiagnostik AG, Bensheim, Germany) and Promonitor ® ELISA kits (Proteomika, Progenika Biopharma, Bizkaia, Spain)] versus standard care for Crohn's disease (CD). Multiple electronic databases were searched from inception to December 2014 in order to identify primary studies and meta-analyses. Patients with moderate to severe active CD treated with infliximab (IFX) (Remicade ® , Merck Sharp & Dohme Ltd, Kenilworth, NJ, USA) or adalimumab (ADA) (Humira ® , AbbVie Inc., North Chicago, IL, USA). Monitoring of serum anti-TNF-α (IFX or ADA) and/or of anti-drug antibody levels using test assays with a test-treatment algorithm. Standard care. Any patient-related outcome, test agreement and cost-effectiveness estimates. The quality assessments used recognised checklists (Quality Assessment of Diagnostic Accuracy Studies-2, Cochrane, Philips and Consolidated Health Economic Evaluation Reporting Standards). Evidence was synthesised using narrative review and meta-analysis. A Markov model was built in TreeAge Pro 2013 (TreeAge Software, Inc., Williamstown, MA, USA). The model had a 4-week cycle and a 10-year time horizon, adopted a NHS and Personal Social Services perspective and used a linked evidence approach. Costs were adjusted to 2013/14 prices and discounted at 3.5%. We included 68 out of 2434 and 4 out of 2466 studies for the clinical effectiveness and cost-effectiveness reviews, respectively. Twenty-three studies comparing test methods were identified. Evidence on test concordance was sparse and contradictory, offering scant data for a linked evidence approach. Three studies [two randomised controlled trials (RCTs) and one

  19. O papel do Fator de Necrose Tumoral Alfa (TNF-alfa no processo de erosão óssea presente no colesteatoma adquirido da orelha média The role of Tumor Necrosis Factor -Alpha (TNF- alpha in bone resorption present in middle ear cholesteatoma

    Directory of Open Access Journals (Sweden)

    Rodrigo Faller Vitale

    2007-02-01

    Full Text Available O colesteatoma adquirido da orelha média causa erosão óssea, com altas taxas de morbidade e mortalidade. O TNF-alfa (TNF-alfa lambda uma das principais citocinas envolvidas neste processo. OBJETIVO: Avaliar o papel do TNF-alfa na reabsorsão óssea e a ação dele no colesteatoma. MATERIAL E MÉTODOS: Foi realizado um levantamento e uma revisão crítica da literatura. RESULTADOS: Todos os autores estudados concordam com a importância do TNF-alfa no processo de reabsorção óssea presente no colesteatoma e com o grau de destruição observado. Diferentes trabalhos demonstraram que o TNF-alfa é capaz de provocar erosão óssea, através de diferentes vias de ação. Ele pode estimular a diferenciação e a maturação dos osteoclastos ou, ainda, agir na matriz óssea expondo-a à ação dos osteoclastos. Existe a possibilidade de inibir a ação do TNF-alfa, diminuindo seus efeitos e prevenindo a perda óssea em doenças como a artrite reumatóide. Não existe, entretanto, trabalhos específicos em colesteatoma. Não existe consenso sobre a sua localização. Estas diferenças, provavelmente, ocorrem devido à distribuição dos receptores. CONCLUSÃO: O TNF-alfa, presente no colesteatoma promove a reabsorsão óssea, juntamente com outras citocinas (RANKL e IL-1, estando relacionado com a presença de complicações.Cholesteatoma may cause bone erosion, with high morbidity and mortality rates. Tumor Necrosis Factor -Alpha (TNF-a is one of the main cytokines involved in this process. Our goal was to evaluate the role of TNF-a in Bone Resorption and its effect on cholesteatoma. MATERIAL AND METHODS: analysis and critical literature review. RESULTS: Different studies have demonstrated that TNF-a is capable of causing bone erosion. It may stimulate the differentiation and maturation of osteoclasts or it may act on the bone matrix, exposing it to the action of the osteoclasts. It is possible to inhibit TNF-a, reducing its effects and prevent

  20. Triggered Urine Interleukin-6 Correlates to Severity of Symptoms in Nonfebrile Lower Urinary Tract Infections.

    Science.gov (United States)

    Sundén, Fredrik; Butler, Daniel; Wullt, Björn

    2017-07-01

    Objective diagnosis of symptomatic urinary tract infections in patients prone to asymptomatic bacteriuria is compromised by local host responses that are already present and the positive urine culture. We investigated interleukin-6 as a biomarker for nonfebrile urinary tract infection severity and diagnostic thresholds for interleukin-6 and 8, and neutrophils to differentiate between asymptomatic bacteriuria and urinary tract infection. Patients with residual urine and neurogenic bladders due to spinal lesions included in a long-term Escherichia coli 83972 asymptomatic bacteriuria inoculation trial were monitored for 2 years. Symptom scoring and urine sampling to estimate interleukin-6 and 8, and neutrophils were performed regularly monthly and at urinary tract infection episodes. Patients were followed in the complete study for a mean of 19 months (range 10 to 27) and those with asymptomatic bacteriuria with E. coli 83972 were followed a mean of 11 months (range 4 to 19). A total of 37 nonfebrile urinary tract infection episodes with complete data on interleukin-6 and 8, neutrophils and symptom scoring were documented. Interleukin-6 was the only marker that persistently increased during urinary tract infection compared to asymptomatic bacteriuria in pooled and paired intra-individual comparisons (p urinary tract infection symptoms (p urinary tract infection episodes. However, in urinary tract infections with worse symptoms interleukin-6 and neutrophils demonstrated equal good/excellent outcomes. Triggered interleukin-6 correlated to urinary tract infection symptom severity and demonstrated a promising differential diagnostic capacity to discriminate urinary tract infection from asymptomatic bacteriuria. Future studies should explore interleukin-6 as a biomarker of urinary tract infection severity and assess the treatment indication in nonfebrile urinary tract infections. Copyright © 2017 American Urological Association Education and Research, Inc. Published by

  1. Measurement of Interleukin-6 in Cerebrospinal Fluid for the Diagnosis of Bacterial Meningitis.

    Science.gov (United States)

    Dano, Ibrahim Dan; Sadou, Hassimi; Issaka, Bassira; Oukem-Boyer, Odile Ouwe Missi

    It is assessed whether the measurement of interleukin-6 in the cerebrospinal fluid can serve as a biomarker for the diagnosis of bacterial meningitis. Cerebrospinal fluid was obtained from 152 patients aged 0-15 years suspected of having meningitis. These patients were classified into the following groups: Bacterial meningitis (n = 85), aseptic meningitis (n = 35) and non-meningitis/control (n = 32) based on leukocyte count and bacterial identification by culture and molecular biology. Interleukin-6 concentrations in cerebrospinal fluid were measured by enzyme-linked immunosorbent assay. This study found a significant difference of the mean cerebrospinal fluid interleukin-6 level (p≤0.01) between patients with bacterial meningitis (3,538.69±2,560.78 pg mL -1) and patients with aseptic meningitis (332.51±470.69 pg mL -1) or those of the control group (205.83±79.39 pg mL -1). There was also a significant difference of the mean cerebrospinal fluid interleukin-6 level between patients with aseptic meningitis and those of the control group. Interleukin-6 had the highest area under the ROC curve: 0.94 (95% confidence interval: 0.901-0.979) compared to that of cerebrospinal fluid glucose and total protein. At a cut-off value of 1,065.96 pg mL -1, interleukin-6 had a sensitivity of 76.2% and specificity of 100%. Interleukin-6 is a potential biomarker for the differential diagnosis of meningitis.

  2. Interleukin-6 and lung inflammation: evidence for a causative role in inducing respiratory system resistance increments.

    Science.gov (United States)

    Rubini, Alessandro

    2013-10-01

    Interleukin-6 is a multifunctional cytokine that has been shown to be increased in some pathological conditions involving the respiratory system such as those experimentally induced in animals or spontaneously occurring in humans. Experimental data demonstrating that interleukin-6 plays a significant role in commonly occurring respiratory system inflammatory diseases are reviewed here. Those diseases, i.e. asthma and chronic obstructive pulmonary disease, are characterised by mechanical derangements of the respiratory system, for the most part due to increased elastance and airway resistance. Recent findings showing that interleukin-6 has a causative role in determining an increase in airway resistance are reviewed. The end-inflation occlusion method was used to study the mechanical properties of the respiratory system before and after interleukin-6 administration. The cytokine was shown to induce significant, dose-dependent increments in both the resistive pressure dissipation due to frictional forces opposing the airflow in the airway (ohmic resistance) and the additional resistive pressure dissipation due to the visco-elastic properties of the system, i.e. stress relaxation (visco-elastic resistance). There were no alterations in respiratory system elastance. Even when administered to healthy mammals, interleukin-6 determines a significant effect on respiratory system resistance causing an increase in the mechanical work of breathing during inspiration. IL-6 hypothetically plays an active role in the pathogenesis of respiratory system diseases and the mechanisms that may be involved are discussed here.

  3. Phosphatidylinositol 3-Kinase and Protein Kinase C Contribute to the Inhibition by Interleukin 6 of Phosphoenolpyruvate Carboxykinase Gene Expression in Cultured Rat Hepatocytes

    DEFF Research Database (Denmark)

    Christ, Bruno; Yazici, Emine; Nath, Annegret

    2000-01-01

    Gluconeogenesis, hepatocytes, interleukin 6, liver, phosphoinositide 3-kinase, phosphoenolpyruvate carboxykinase......Gluconeogenesis, hepatocytes, interleukin 6, liver, phosphoinositide 3-kinase, phosphoenolpyruvate carboxykinase...

  4. Interleukin-6

    DEFF Research Database (Denmark)

    Reihmane, Dace; Dela, Flemming

    2014-01-01

    as anti-inflammatory properties of IL-6. Since the first report of acute exercise-induced increase in plasma IL-6 in the early 1990s, scientists have tried to elucidate the factors that influence the magnitude of change of plasma IL-6, as well as the possible biological roles of this cytokine. Evidence...

  5. Interleukin-6

    DEFF Research Database (Denmark)

    Andersen, Mette Bisgaard; Pingel, Jessica; Kjær, Michael

    2011-01-01

    Human connective tissue, e.g., tendon, responds dynamically to physical activity, with collagen synthesis being increased after both acute and prolonged exercise or training. Markers of collagen synthesis and degradation as well as concentration of several potential growth factors have been shown...

  6. S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

    DEFF Research Database (Denmark)

    de Nully Brown, P; Jensen, P O; Diamant, Marcus

    1998-01-01

    The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S-ph...

  7. Induction of plasma interleukin-6 by circulating adrenaline in the rat

    NARCIS (Netherlands)

    DeRijk, R. H.; Boelen, A.; Tilders, F. J.; Berkenbosch, F.

    1994-01-01

    Adrenaline, which is secreted from the adrenal medulla during stress, is considered to be involved in the control of inflammation and immune responses. Therefore, we studied the effects of adrenaline on the plasma levels of one of the major pro-inflammatory cytokines, interleukin-6 (IL-6). Here we

  8. Synergistic inhibition of interleukin-6 production in adipose stem cells by tart cherry anthocyanins and atorvastatin

    Science.gov (United States)

    Studies have shown positive correlations between inflammatory cytokines such as interleukin-6 (IL-6) and the development of chronic diseases including cardiovascular disease by activating C-reactive prorein (CRP). Both atorvastatin calcium (lipitor) as well as flavonoid rich fruit such as tart cherr...

  9. Early Dynamics of P-selectin and Interleukin 6 Predicts Outcomes in Ischemic Stroke

    DEFF Research Database (Denmark)

    Pusch, Gabriella; Debrabant, Birgit; Molnar, Tihamer

    2015-01-01

    to poststroke infection, death, and functional outcome, and assessed the ability of the models to predict each outcome. RESULTS: Interleukin 6 (IL-6) levels and change of IL-6 concentrations by 72 hours correlated with the size of tissue damage indicated by S100B titers. Levels of IL-6 and P-selectin at 72...

  10. Increased Levels of YKL-40 and Interleukin 6 in Patients With Chronic Pancreatitis and Secondary Diabetes

    DEFF Research Database (Denmark)

    Hansen, Morten; Nielsen, Anders Rinnov; Vilsbøll, Tina

    2012-01-01

    Circulating levels of YKL-40 and interleukin 6 (IL-6) are elevated in patients with type 2 diabetes. We aimed to evaluate YKL-40 levels in patients with chronic pancreatitis (CP) with and without secondary diabetes mellitus (DM) to investigate whether elevated plasma YKL-40 could play a primary...

  11. Oral contraception does not alter typical post-exercise interleukin-6 and hepcidin levels in females

    NARCIS (Netherlands)

    Sim, M.; Dawson, B.; Landers, G.; Swinkels, D.W.; Tjalsma, H.; Yeap, B.B.; Trinder, D.; Peeling, P.

    2015-01-01

    OBJECTIVES: The post-exercise interleukin-6 (IL-6) and hepcidin response was investigated during the hormone-deplete and hormone-replete phases of an estradiol and progestogen regulated oral contraceptive cycle (OCC). DESIGN: Counterbalanced, repeated measures cross-over study. METHODS: Ten active

  12. Interleukin-6 and Delayed Onset Muscle Soreness Do Not Vary during the Menstrual Cycle

    Science.gov (United States)

    Chaffin, Morgan E.; Berg, Kris E.; Meendering, Jessica R.; Llewellyn, Tamra L.; French, Jeffrey A.; Davis, Jeremy E.

    2011-01-01

    The purpose of this study was to determine if a difference in interleukin-6 (IL-6) and delayed onset muscles soreness (DOMS) exists in two different phases of the menstrual cycle. Nine runners performed one 75-min high-intensity interval running session during the early follicular (EF) phase and once during the midluteal (ML) phase of the…

  13. Interleukin-6 in CAPD patients without peritonitis: relationship to the intrinsic permeability of the peritoneal membrane

    NARCIS (Netherlands)

    Zemel, D.; ten Berge, R. J.; Struijk, D. G.; Bloemena, E.; Koomen, G. C.; Krediet, R. T.

    1992-01-01

    We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected

  14. Modulation of chronic excessive interleukin-6 production in multiple myeloma does not affect thyroid hormone concentrations

    NARCIS (Netherlands)

    van Zaanen, H. C.; Romijn, J. A.; Sauerwein, H. P.; Lokhorst, H. M.; Warnaar, S. O.; Aarden, L. A.; Endert, E.; van Oers, M. H.

    1997-01-01

    Interleukin-6 (IL6) is believed to be involved in alterations of thyroid hormone metabolism in acute nonthyroidal illness. To evaluate the effects of IL6 on thyroid hormone metabolism in a chronic IL6-mediated disease, we measured thyroid hormone concentrations in multiple myeloma patients treated

  15. Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Johansen, Julia S

    2012-01-01

    Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal cells and tumor cells, including melanoma cells. The specific biological function of IL-6 in melanoma is unknown. The present study examined whether the serum concentration of IL-6 can predict prognosis in patients...

  16. Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Ogston, N. C.; Karastergiou, K.; Hosseinzadeh-Attar, M. J.; Bhome, R.; Madani, R.; Stables, M.; Gilroy, D.; Flachs, Pavel; Hensler, Michal; Kopecký, Jan; Mohamed-Ali, V.

    2008-01-01

    Roč. 32, č. 12 (2008), s. 1807-1815 ISSN 0307-0565 Grant - others:Wellcome trust(XE) 070821/Z/03/Z; EC(XE) LSHM-CT-2004-005272 Institutional research plan: CEZ:AV0Z50110509 Keywords : interleukin-6 * adipose tissue * aspirin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.640, year: 2008

  17. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies

    NARCIS (Netherlands)

    Sarwar, Nadeem; Butterworth, Adam S.; Freitag, Daniel F.; Gregson, John; Willeit, Peter; Gorman, Donal N.; Gao, Pei; Saleheen, Danish; Rendon, Augusto; Nelson, Christopher P.; Braund, Peter S.; Hall, Alistair S.; Chasman, Daniel I.; Tybjærg-Hansen, Anne; Chambers, John C.; Benjamin, Emelia J.; Franks, Paul W.; Clarke, Robert; Wilde, Arthur A. M.; Trip, Mieke D.; Steri, Maristella; Witteman, Jacqueline C. M.; Qi, Lu; van der Schoot, C. Ellen; de Faire, Ulf; Erdmann, Jeanette; Stringham, Heather M.; Koenig, Wolfgang; Rader, Daniel J.; Melzer, David; Reich, David; Psaty, Bruce M.; Kleber, Marcus E.; Panagiotakos, Demosthenes B.; Willeit, Johann; Wennberg, Patrik; Woodward, Mark; Adamovic, Svetlana; Rimm, Eric B.; Meade, Tom W.; Gillum, Richard F.; Shaffer, Jonathan A.; Hofman, Albert; Onat, Altan; Sundström, Johan; Wassertheil-Smoller, Sylvia; Mellström, Dan; Gallacher, John; Cushman, Mary; Tracy, Russell P.; Kauhanen, Jussi; Karlsson, Magnus; Salonen, Jukka T.; Wilhelmsen, Lars; Amouyel, Philippe; Cantin, Bernard; Best, Lyle G.; Ben-Shlomo, Yoav; Manson, JoAnn E.; Davey-Smith, George; de Bakker, Paul I. W.; O'Donnell, Christopher J.; Wilson, James F.; Wilson, Anthony G.; Assimes, Themistocles L.; Jansson, John-Olov; Ohlsson, Claes; Tivesten, Åsa; Ljunggren, Östen; Reilly, Muredach P.; Hamsten, Anders; Ingelsson, Erik; Cambien, Francois; Hung, Joseph; Thomas, G. Neil; Boehnke, Michael; Schunkert, Heribert; Asselbergs, Folkert W.; Kastelein, John J. P.; Gudnason, Vilmundur; Salomaa, Veikko; Harris, Tamara B.; Kooner, Jaspal S.; Allin, Kristine H.; Nordestgaard, Børge G.; Hopewell, Jemma C.; Goodall, Alison H.; Ridker, Paul M.; Hólm, Hilma; Watkins, Hugh; Ouwehand, Willem H.; Samani, Nilesh J.; Kaptoge, Stephen; Di Angelantonio, Emanuele; Harari, Olivier; Danesh, John; Quertermous, Thomas; Go, Alan S.; Hlatky, Mark A.; Knowles, Joshua W.; Smith, Albert V.; Chrysohoou, Christina; Pitsavos, Christos; Stefanadis, Christodoulos; Balmforth, Anthony J.; Thompson, John R.; Sivapalaratnam, Suthesh; Maiwald, Stephani; Basart, Hanneke; Motazacker, Mahdi; de Jong, Jonas S. S. G.; Dekker, Lucas R. C.; Tanck, Michael; Bezzina, Connie R.; Whincup, Peter H.; Morris, Richard W.; Wannamethee, S. Goya; Kiechl, Stefan; Yarnell, John W. G.; Lowe, Gordon; Rumley, Ann; Mukamal, Kenneth J.; Havulinna, Aki S.; Lokki, Marja-Liisa; Nieminen, Markku S.; Ripatti, Samuli; Sinisalo, Juha; McQuillan, Brendan M.; Beilby, John P.; Thompson, Peter L.; Thorleifsson, Guðmar; Thorgeirsson, Guðmundur; Thorsteinsdóttir, Unnur; Stefansson, Kari; Jula, Antti; Männistö, Satu; Perola, Markus; Tikkanen, Emmi; Boer, Jolanda M. A.; Onland-Moret, N. Charlott; van der Schouw, Yvonne T.; Verschuren, W. M. Monique; Jansson, Jan-Håkan; Dupuis, Josée; Fontes, João D.; Yin, Xiaoyan; Tuomilehto, Jaakko; Koenig, Inke R.; Nahrstaedt, Janja; Loley, Christina; Stark, Klaus; Willenborg, Christina; Hengstenberg, Christian; Schreiber, Stefan; Preuss, Michael; Barroso, Inês; Hallmans, Göran; Shungin, Dmitry; Cheng, Kar Keung; Lam, Tai Hing; Jiang, Chao Chiang; Pai, Jennifer; Collins, Rory; Parish, Sarah; Armitage, Jane; Jackson, Anne; Hveem, Kristian; Wiggins, Kerri L.; Heckbert, Susan R.; Smith, Nicholas L.; Bis, Joshua C.; Ferrucci, Luigi; Guralnik, Jack M.; Bandinelli, Stefania; Singleton, Andrew B.; Tuomainen, Tomi-Pekka; Kurl, Sudhir; Zhang, Weihua; Kooner, Angad S.; Das, Debashis; März, Winfried; Scharnagl, Hubert; Böhm, Bernhard O.; Winkelmann, Bernhard R.; Folsom, Aaron R.; Shea, Steven J.; Laakso, Markku; Kuusisto, Johanna; Baumert, Jens; Thorand, Barbara; Illig, Thomas; Meisinger, Christa; Rosengren, Annika; Karlsson, Magnus K.; Hu, Frank B.; Hankinson, Susan E.; Davidson, Karina W.; Fraser, Ross; Wild, Sarah; Campbell, Harry; Qasim, Atif; Qu, Liming; Li, Mingyao; Lind, Lars; Syvänen, Ann-Christine; Arveiler, Dominique; Farrall, Martin; Peden, John F.; Deloukas, Panos; Sheikh, Nasir; Rasheed, Asif; Dagenais, Gilles R.; Dehghan, Abbas; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Abecasis, Goncalo R.; Cucca, Francesco; Sanna, Serena; Uda, Manuela; Schlessinger, David; Sabater-Lleal, Maria; Silveira, Angela; Gigante, Bruna; Howard, Barbara V.; Basu, Samar; Rose, Lynda M.; Buring, Julie

    2012-01-01

    Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we

  18. RECOMBINANT HUMAN INTERLEUKIN-6 INDUCES A RAPID AND REVERSIBLE ANEMIA IN CANCER-PATIENTS

    NARCIS (Netherlands)

    NIEKEN, J; MULDER, NH; VELLENGA, E; LIMBURG, PC; PIERS, DA; DEVRIES, EGE

    1995-01-01

    Initial studies have shown that recombinant human interleukin-6 (rhIL-6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II

  19. Endotoxin-induced uveitis in the rat. The significance of intraocular interleukin-6

    NARCIS (Netherlands)

    Hoekzema, R.; Verhagen, C.; van Haren, M.; Kijlstra, A.

    1992-01-01

    The potential role of interleukin-6 (IL-6) was studied as an inflammatory mediator of endotoxin (or lipopolysaccharide [LPS])-induced uveitis (EIU) in the rat. In young Lewis rats, levels of intraocular IL-6, but not serum IL-6, correlated with the severity of uveitis and with aqueous humor protein

  20. Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis.

    Science.gov (United States)

    García-Hernández, Pablo; Prieto, Belén; Martínez-Morillo, Eduardo; Rodríguez, Verónica; Álvarez, Francisco V

    2016-01-01

    Microbiological culture of cerebrospinal fluid is the gold standard to differentiate between aseptic and bacterial meningitis, but this method has low sensitivity. A fast and reliable new marker would be of interest in clinical practice. Interleukin-6, secreted by T cells in response to meningeal pathogens and quickly delivered into cerebrospinal fluid, was evaluated as a marker of acute meningitis. A total of 150 cerebrospinal fluid samples were analysed by an electrochemiluminescence method, selected according to patient diagnosis: (a) bacterial meningitis confirmed by positive culture (n = 26); (b) bacterial meningitis with negative culture or not performed (n = 15); (c) viral meningitis confirmed by polymerase chain reaction or immunoglobulin G determination (n = 23); (d) viral meningitis with polymerase chain reaction negative or not performed (n = 42); and (e) controls (n = 44). Cerebrospinal fluid interleukin-6 concentration showed significant differences between all pathologic groups and the control group (P meningitis, interleukin-6 showed an area under the curve of 0.937 (95% confidence intervals: 0.895-0.978), significantly higher than those of classical biomarkers. An interleukin-6 cutoff of 1418 pg/mL showed 95.5% sensitivity and 77.5% specificity, whereas a value of 15,060 pg/mL showed 63.6% sensitivity and 96.7% specificity, for diagnosis of bacterial meningitis. Interleukin-6 measured by electrochemiluminescence method is a promising marker for early differentiation between aseptic and bacterial meningitis. More studies are needed to validate clinical implications for future practice in an emergency laboratory. © The Author(s) 2015.

  1. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul

    2010-01-01

    with tumor necrosis factor-alpha (TNF alpha) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n = 32, and psoriatic arthritis, n = 17) initiating TNF alpha inhibitor therapy (infliximab, n = 38...

  2. The interleukin-6 receptor as a target for prevention of coronary heart disease : a mendelian randomisation analysis

    NARCIS (Netherlands)

    Swerdlow, Daniel I.; Holmes, Michael V.; Kuchenbaecker, Karoline B.; Engmann, Jorgen E. L.; Shah, Tina; Sofat, Reecha; Guo, Yiran; Chung, Christina; Peasey, Anne; Ster, Roman Pfi; Mooijaart, Simon P.; Ireland, Helen A.; Leusink, Maarten; Langenberg, Claudia; Li, KaWah; Palmen, Jutta; Howard, Philip; Cooper, Jackie A.; Drenos, Fotios; Hardy, John; Nalls, Michael A.; Li, Yun Rose; Lowe, Gordon; Stewart, Marlene; Bielinski, Suzette J.; Peto, Julian; Timpson, Nicholas J.; Gallacher, John; Dunlop, Malcolm; Houlston, Richard; Tomlinson, Ian; Tzoulaki, Ioanna; Luan, Jian'an; Boer, Jolanda M. A.; Forouhi, Nita G.; Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.; Schnabel, Renate B.; Hubacek, Jaroslav A.; Kubinova, Ruzena; Baceviciene, Migle; Tamosiunas, Abdonas; Pajak, Andrzej; Topor-Madry, Roman; Malyutina, Sofi A.; Baldassarre, Damiano; Sennblad, Bengt; Tremoli, Elena; de Faire, Ulf; Ferrucci, Luigi; Bandenelli, Stefania; Tanaka, Toshiko; Meschia, James F.; Singleton, Andrew; Navis, Gerjan; Mateo Leach, Irene; Bakker, Stephan J. L.; Gansevoort, Ron T.; Ford, Ian; Epstein, Stephen E.; Burnett, Mary Susan; Devaney, Joe M.; Jukema, J. Wouter; Westendorp, Rudi G. J.; de Borst, Gert Jan; van der Graaf, Yolanda; de Jong, Pim A.; Maitland-van der Zee, Anke-Hilse; Klungel, Olaf H.; de Boer, Anthonius; Doevendans, Pieter A.; Stephens, Jeffrey W.; Eaton, Charles B.; Robinson, Jennifer G.; Manson, JoAnn E.; Fowkes, F. Gerry R.; Frayling, Timothy M.; Price, Jackie F.; Whincup, Peter H.; Morris, Richard W.; Lawlor, Debbie A.; Smith, George Davey; Ben-Shlomo, Yoav; Redline, Susan; Lange, Leslie A.; Kumari, Meena; Wareham, Nick J.; Verschuren, W. M. Monique; Benjamin, Emelia J.; Whittaker, John C.; Hamsten, Anders; Dudbridge, Frank; Delaney, J. A. Chris; Wong, Andrew; Kuh, Diana; Hardy, Rebecca; Castillo, Berta Almoguera; Connolly, John J.; van der Harst, Pim; Brunner, Eric J.; Marmot, Michael G.; Wassel, Christina L.; Humphries, Steve E.; Talmud, Philippa J.; Kivimaki, Mika; Asselbergs, Folkert W.; Voevoda, Mikhail; Bobak, Martin; Pikhart, Hynek; Wilson, James G.; Hakonarson, Hakon; Reiner, Alex P.; Keating, Brendan J.; Sattar, Naveed; Hingorani, Aroon D.; Casas, Juan Pablo

    2012-01-01

    Background A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation.

  3. Source and kinetics of interleukin-6 in humans during exercise demonstrated by a minimally invasive model

    DEFF Research Database (Denmark)

    Toft, Anders Dyhr; Falahati, Ali; Steensberg, Adam

    2011-01-01

    The objective of this study was to use a novel and non-invasive model to explore whether: (1) exercise-induced increases in systemic levels of interleukin-6 (IL-6) and other cytokines can be ascribed to local production in working muscle; and (2) how acute release of retained blood from an exerci......The objective of this study was to use a novel and non-invasive model to explore whether: (1) exercise-induced increases in systemic levels of interleukin-6 (IL-6) and other cytokines can be ascribed to local production in working muscle; and (2) how acute release of retained blood from...... was inhibited for 18 min by inflating a cuff around the thigh as proximally as possible immediately following exercise. On the control occasion venous outflow was not inhibited. Venous blood samples were collected from an arm vein at 2-min intervals after exercise. During inhibition of venous outflow from...

  4. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J

    1999-01-01

    and reactive astrocytes surrounding the lesion site. In addition, expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and metallothionein-I+II (MT-I+II) were increased in these cells, while the brain-specific MT-III was only moderately upregulated. In IL-6-/- mice, however, the response......Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...... response in the brain following disruption of the blood-brain barrier (BBB), we examined the effects of a focal cryo injury to the fronto-parietal cortex in interleukin-6-deficient (IL-6-/-) and normal (IL-6+/+) mice. In IL-6+/+ mice, brain injury resulted in the appearance of brain macrophages...

  5. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J

    2001-01-01

    and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus......The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice......, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid...

  6. Interleukin 6 modulates acetylcholinesterase activity of brain neurons; Effet de l`interleukine 6 sur l`activite de l`acetylcholinesterase des neurones centraux

    Energy Technology Data Exchange (ETDEWEB)

    Clarencon, D.; Multon, E.; Galonnier, M.; Estrade, M.; Fournier, C.; Mathieu, J.; Mestries, J.C.; Testylier, G.; Fatome, M.

    1995-12-31

    Classically, radiation injuries results in a peripheral inflammatory process, and we have previously observed an early systemic interleukin 6 (IL-6) release following whole-body irradiation. Besides, we have demonstrated an early decrease of rat or primate brain acetylcholinesterase (AChE) activity a gamma exposure. The object of the present study is to find possible IL-6 systemic effects on the brain AChE activity. We show that, though intravenous (i.v.) or intra-cerebro-ventricular (ICV) injection of IL-6 can induce a drop in rat brain AChE activity, this cytokine induces only a slight decrease of the AChE release in cultured brain cells. (author). 3 refs.

  7. Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells

    Czech Academy of Sciences Publication Activity Database

    Hubáčková, Soňa; Krejčíková, Kateřina; Bartek, Jiří; Hodný, Zdeněk

    2012-01-01

    Roč. 287, č. 32 (2012), s. 26702-26714 ISSN 0021-9258 R&D Projects: GA ČR GA204/08/1418 Grant - others:Novo Nordisk(DK) R153-A12997; EK(XE) 223575 Institutional support: RVO:68378050 Keywords : cancer tumor promoter * DNA-binding protein * protein phosphorylation * tyrosine protein kinase * interleukin-6 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.651, year: 2012

  8. Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study

    OpenAIRE

    Puzianowska-Ku?nicka, Monika; Owczarz, Magdalena; Wieczorowska-Tobis, Katarzyna; Nadrowski, Pawel; Chudek, Jerzy; Slusarczyk, Przemyslaw; Skalska, Anna; Jonas, Marta; Franek, Edward; Mossakowska, Malgorzata

    2016-01-01

    Background In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65?years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly. Results IL-6 and CRP levels syst...

  9. Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Charlotte; Keller, Pernille

    2003-01-01

    Interleukin-6 (IL-6) is produced by many different cell types. Human skeletal muscles produce and release high amounts of IL-6 during exercise; however, the cell source of origin in the muscle is not known. Therefore, we studied the protein expression of IL-6 by immunohistochemistry in human musc...... are the dominant cell source of exercise-induced release of IL-6 from working muscle....

  10. Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion

    DEFF Research Database (Denmark)

    Vozarova, B; Weyer, C; Hanson, K

    2001-01-01

    Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined w...... whether circulating plasma IL-6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes....

  11. Association of Gene Polymorphisms in Interleukin 6 in Infantile Bronchial Asthma.

    Science.gov (United States)

    Babusikova, Eva; Jurecekova, Jana; Jesenak, Milos; Evinova, Andrea

    2017-07-01

    The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C (rs1800795) and at -572G/C (rs1800796) in relation to asthma in children. Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis. We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR=3.4, 95% CI: 2.045-5.638, P10 -7 ). Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic polymorphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. The Link Between Oxidative Stress Response and Tumor Necrosis ...

    African Journals Online (AJOL)

    Dr Olaleye Samuel

    Factor-Alpha (TNF-alpha) in Hepatic Tissue of Rats With Induced. Thyroid Dysfunction. 1Suzan Hazzaa ... Tumor necrosis factor-alpha (TNF-α) is a cytokine with numerous immunological and metabolic activities. Several studies ... However, when free radical generation exceeds the antioxidant capacity of cells, oxidative ...

  13. Single intradiscal injection of the interleukin-6 receptor antibody tocilizumab provides short-term relief of discogenic low back pain; prospective comparative cohort study.

    Science.gov (United States)

    Sainoh, Takeshi; Orita, Sumihisa; Miyagi, Masayuki; Inoue, Gen; Yamauchi, Kazuyo; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Inage, Kazuhide; Sato, Jun; Nakata, Yukio; Aoki, Yasuchika; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    Inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, are gaining attention as important etiologic factors associated with discogenic low back pain. We conducted a prospective cohort study to evaluate the efficacy and safety of intradiscal injection of the interleukin-6 receptor antibody tocilizumab in patients with discogenic low back pain. Thirty-two consecutive patients were intradiscally injected with 2 mL of 0.5% bupivacaine (control group). Another 31 consecutive patients were intradiscally injected with 40 mg tocilizumab and 1-2 mL of 0.5% bupivacaine (tocilizumab group) at the same time. Prior to treatment, the vertebral origin of low back pain was confirmed in all patients based on pain provocation during discography and pain relief with 1 mL of 1% xylocaine. Numeric rating scale and Oswestry disability index scores were used to evaluate pain level before and after treatment between the 2 groups. The association between pain relief with tocilizumab and intervertebral disc degeneration grade was also determined. At the end of the study (8 weeks after treatment), 30 patients in each group were evaluable. In the tocilizumab group, numeric rating scale and Oswestry disability index scores improved significantly at 2 and 4 weeks after treatment, respectively. Intervertebral disc degeneration was not associated with improvement of numeric rating scale score in the tocilizumab group. Local infection (i.e., discitis) was observed in 1 patient in the tocilizumab group. The results demonstrate the clinical relevance of interleukin-6 in discogenic low back pain. Intradiscal tocilizumab injection was shown to exert a short-term analgesic effect in patients with discogenic low back pain. Further research is required to determine the long-term effects of intradiscal tocilizumab therapy in patients with discogenic low back pain. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  14. Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells

    Directory of Open Access Journals (Sweden)

    Dimitriades-Schmutz Beatrice

    2009-02-01

    Full Text Available Abstract Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6 and the neurotrophin (NT Nerve Growth Factor (NGF for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold, regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold, growth differentiation factor 15 (GDF15; 80-fold, platelet-derived growth factor alpha (PDGFA; 69-fold, growth hormone releasing hormone (GHRH; 30-fold, adenylate cyclase activating polypeptide (PACAP; 20-fold and hepatocyte growth factor (HGF; 5-fold. NGF recruits GDF15 (131-fold, transforming growth factor beta 1 (TGFB1; 101-fold and brain-derived neurotrophic factor (BDNF; 89-fold. Both stimuli activate growth-associated protein 43 (GAP-43 indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold and early growth response 1 (Egr1/Zif268; 3-fold known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell

  15. Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Jakobsen, P H; Moon, R; Ridley, R G

    1993-01-01

    of infected erythrocytes. These results indicate that the RAP-1 and MSP-1 proteins themselves do not stimulate the production of TNF. Instead, other components associating with these exoantigens may be responsible for the TNF production. Mouse antisera blocking TNF production stimulated by P. yoelii......P. falciparum merozoite antigens, merozoite surface protein-1 (MSP-1) and rhoptry associated protein-1 (RAP-1), were shown to be liberated into the supernatant of in vitro parasite cultures and to be included in the endotoxin-like exoantigen complex, previously designated Ag7. Material affinity...... exoantigens also blocked TNF production stimulated by material affinity purified from P. falciparum culture supernatants using RAP-1 specific monoclonal antibody, indicating the conserved structure of the TNF inducing component....

  16. Effect of intraoperative intravenous lidocaine on pain and plasma interleukin-6 in patients undergoing hysterectomy

    Directory of Open Access Journals (Sweden)

    Caio Marcio Barros de Oliveira

    2015-04-01

    Full Text Available BACKGROUND AND OBJECTIVES: Interleukin-6 is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma interleukin-6 after hysterectomy. METHOD: A prospective, randomized, comparative, double-blind study with 40 patients, aged 18-60 years. G1 received lidocaine (2 mg kg-1 h-1 or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24 h, first analgesic request, and dose of morphine in 24 h were evaluated. Interleukin-6 was measured before starting surgery (T0, 5 h after the start (T5, and 24 h after the end of surgery (T24. RESULTS: There was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0 ± 104.4 min than in G1 (26.7 ± 23.3 min. There was no difference in supplemental dose of morphine between G1 (23.5 ± 12.6 mg and G2 (18.7 ± 11.3 mg. There were increased concentrations of IL-6 in both groups from T0 to T5 and T24. There was no difference in IL-6 dosage between groups. Lidocaine concentration was 856.5 ± 364.1 ng mL-1 in T5 and 30.1 ± 14.2 ng mL-1 in T24. CONCLUSION: Intravenous lidocaine (2 mg kg-1 h-1 did not reduce pain severity and plasma levels of IL-6 in patients undergoing abdominal hysterectomy.

  17. Diagnostic performance of interleukin-6 and interleukin-8 for bacterial meningitis: a meta-analysis

    Science.gov (United States)

    Yao, Rong; Cao, Yu; Chen, Yao; Zeng, Zhi

    2015-01-01

    This study aimed to summarize the overall diagnostic performance of interleukin-6 and interleukin-8 in cerebrospinal fluid for bacterial meningitis through meta-analysis due to inconclusive results reported. Literature search was performed in PubMed and Embase to identify eligible studies. Data were retrieved and sensitivity, specificity, positive likelihood ratio/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary receiver operating characteristic curve and the area under the curve (AUC) were calculated to evaluate their overall test performances. Thirteen studies were included for present meta-analysis. The summary estimates for interleukin-6 in diagnosing bacterial meningitis were: sensitivity, 0.91 (95% CI 0.81-0.96); specificity, 0.93 (95% CI 0.84-0.97); PLR, 12.38 (95% CI 5.42-28.29); NLR, 0.10 (95% CI 0.04-0.21); DOR, 129.76 (95% CI 41.48-405.88); and AUC 0.97 (95% CI 0.95-0.98). The corresponding summary performance estimates for interleukin-8 were as follows: sensitivity, 0.95 (95% CI 0.71-0.99); specificity, 0.89 (95% CI 0.77-0.95); PLR, 8.50 (95% CI, 3.83-18.86); NLR, 0.06 (95% CI 0.01-0.40); DOR, 154.25 (95% CI 14.56-1634.33); and AUC 0.95 (95% CI 0.93-0.97). Measurements of interleukin-6 and interleukin-8 play a valuable role in diagnosing bacterial meningitis. Nevertheless, their results should be interpreted in parallel with the results of routine tests and clinical symptoms. PMID:26221243

  18. Interleukin-6 is not essential for bone turnover in hypothyroid mice.

    OpenAIRE

    Maria Gorska; Jerzy Walecki; Zofia Bondyra; Wlodzimierz Musial; Piotr Mysliwiec; Karol Kaminski; Agnieszkar Nikolajuk; Boguslaw Sawicki; Maria Winnicka; Robert Zbucki; Janusz Mysliwiec

    2008-01-01

    Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by an imbalance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) and osteocalcin in IL-6-deficient mice to assess the role of IL-6 in bone metabolism in hypothyroidism in mice. C57BL/6J (wild-type; WT) and C57BL/6J(IL6-/-Kopf) (IL-6 knock-out; IL6KO) mic...

  19. The Good, the Bad, and the Ugly of interleukin-6 signaling

    Science.gov (United States)

    Fuster, José J; Walsh, Kenneth

    2014-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine with complex roles in inflammation and metabolic disease. While typically regarded as a pro-inflammatory cytokine, multiple studies in the last 20 years have generated conflicting data on the role of IL-6 in inflammation and metabolism. In a recent study in Nature Immunology, Brüning and collaborators demonstrate that IL-6 signaling in myeloid cells attenuates obesity-induced inflammation and insulin resistance by promoting macrophage alternative activation (Mauer et al, 2014). This study unveils a new and surprising anti-inflammatory action of IL-6 and further highlights the complex actions of this cytokine. PMID:24850773

  20. Promotion of Endoplasmic Reticulum-Associated Degradation of Procathepsin D by Human Herpesvirus 8-Encoded Viral Interleukin-6

    OpenAIRE

    Chen, Daming; Nicholas, John

    2015-01-01

    The interleukin-6 homologue (viral interleukin-6 [vIL-6]) of human herpesvirus 8 is implicated in viral pathogenesis due to its proproliferative, inflammatory, and angiogenic properties, effected through gp130 receptor signaling. In primary effusion lymphoma (PEL) cells, vIL-6 is expressed latently and is essential for normal cell growth and viability. This is mediated partly via suppression of proapoptotic cathepsin D (CatD) via cocomplexing of the endoplasmic reticulum (ER)-localized CatD p...

  1. Asociación entre periodontitis crónica, interleuquina -6 (IL-6 e índice de masa corporal (IMC en embarazadas Association between chronic periodontitis, interleukin-6 (IL-6 and body mass index (BMI in pregnant women

    Directory of Open Access Journals (Sweden)

    S Mella

    2011-12-01

    Full Text Available Objetivo: Determinar si la condición clínica periodontal materna, el índice de masa corporal (IMC y su variación durante el embarazo, se asocian con marcadores de inflamación sistémica: interleuquina-6 (IL-6, factor de necrosis tumoral alfa (TNF- y proteína C reactiva (PCR a nivel plasmático. Material y Método: Estudio clínico que analizó una cohorte de 56 embarazadas entre 18 y 38 años de edad (promedio 27.9 ± 7.04 años, derivadas de la unidad de medicina perinatal en el centro de salud docente asistencial (CESA de la Universidad de los Andes. Todas ellas consintieron voluntariamente su participación en el estudio. En cada trimestre de embarazo, se les realizó un examen periodontal completo, consistente en la determinación de los niveles de inserción clínica, profundidad al sondaje, índice de higiene y sangrado en seis sitios por cada pieza dentaria, excluyendo terceros molares. Adicionalmente, en cada control se obtuvieron muestras de sangre periférica para la determinación de los mediadores proinflamatorios mediante técnica de ELISA. El diagnóstico periodontal y los niveles de mediadores inflamatorios fueron relacionados con la variación del IMC durante el embarazo. Resultados: Las embarazadas con periodontitis crónica presentaron una mayor variación y aumento del índice de masa corporal (p=0.039 y niveles de IL-6 (p=0.026 en comparación con las mujeres embarazadas con gingivitis. Conclusiones: En esta serie de pacientes, se demostró una asociación entre el diagnóstico clínico de periodontitis durante el embarazo con un aumento plasmático de IL-6, así como también una asociación entre un aumento del IMC con los niveles plasmáticos de PCR.Objective: To determine if maternal periodontal clinical status, body mass index (BMI and its variation during pregnancy are associated with increased levels of interleukin-6 (IL-6, tumor necrosis factor alpha (TNF- and C-reactive protein (CRP in plasma. Material and

  2. Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists

    International Nuclear Information System (INIS)

    Zhang Songwen; Liu Qiangyuan; Wang Juan; Harnish, Douglas C.

    2009-01-01

    C-reactive protein (CRP), a human acute-phase protein, is a risk factor for future cardiovascular events and exerts direct pro-inflammatory and pro-atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily, plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver, whereas no effect was observed in FXR knockout mice. These data provide new evidence for direct anti-inflammatory properties of FXR.

  3. Modern and Convensional Wound Dressing to Interleukin 1 and Interleukin 6 in Diabetic wound

    Directory of Open Access Journals (Sweden)

    Werna Nontji

    2015-04-01

    Full Text Available Introduction:Holistic wound care is one of the ways to prevent gangrene and amputation, modern wound dressing is more effective than convensional with increasing transforming growth factor and cytokine, especially interleukin. This study aims to identify the effectiveness of Modern and Convensional Wound Dressing to Interleukin 1 (IL-1 and Interleukin 6 (IL-6 in Diabetic wound. Method:A Quasi eksperimental pre-post with control group design was used. The intervention given was modern wound dressing and Control group by convensional wound dressing, This study was conducted in Makassar with 32 samples (16 in intervention group and 16 in control group. Result: The result of Pooled T- test showed that p = 0.00 (p < 0.05, it means that there was signifi cant correlation between modern wound dressing to IL-6 and IL-1 than Convensional wound dressing. Discussion: Process of wound healing was produced growth factor and cytokine (IL-1 and IL-6, it will stimulated by wound dressing, modern wound dressing (Calcium alginat can absorb wound drainage, non oklusive, non adhesif, and autolytic debridement. Keywords: Modern wound dressing, Interleukin 1 (IL-1, Interleukin 6 (IL-6

  4. High interleukin-6 mRNA expression is a predictor of relapse in colon cancer

    DEFF Research Database (Denmark)

    Olsen, Jesper; Kirkeby, Lene T; Olsen, Jørgen

    2015-01-01

    AIM: To investigate the expression of interleukin-6 (IL6) in colon cancer tissue, and to examine if the risk of relapse is influenced by IL6 expression. MATERIALS AND METHODS: Fresh-frozen biopsies from tumor and normal adjacent tissues were taken from patients with colon cancer during surgery an...... for clinicopathological characteristics (Hazard Ratio=2.16, 95% CI=1.07-4.40; pcolon cancer tissue at the transcriptional level and is significantly associated with increased risk of relapse.......AIM: To investigate the expression of interleukin-6 (IL6) in colon cancer tissue, and to examine if the risk of relapse is influenced by IL6 expression. MATERIALS AND METHODS: Fresh-frozen biopsies from tumor and normal adjacent tissues were taken from patients with colon cancer during surgery...... to normal adjacent tissue (pcancer stage. We found a significant association between high IL6 expression and risk of relapse (Hazard Ratio=2.23, 95% CI=1.10-4.53; p

  5. Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6-interleukin-10+ cytokine patterns in st-elevation acute myocardial infarction

    KAUST Repository

    Ammirati, Enrico

    2012-08-29

    RATIONALE: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6) levels or very low-IL-6 levels. OBJECTIVE: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response. METHODS AND RESULTS: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6 STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6 STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6 STEMI and IL-6 STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6 STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6 STEMI and IL-6 STEMI patients compared with controls. IL-6IL-10 STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6IL-10 STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death. CONCLUSIONS: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes

  6. VEGF targeting in mesotheliomas using an interleukin-6 signal inhibitor based on adenovirus gene delivery.

    Science.gov (United States)

    Adachi, Yasuo; Yoshio-Hoshino, Naoko; Aoki, Chieko; Nishimoto, Norihiro

    2010-06-01

    Malignant mesotheliomas reportedly secrete interleukin-6 (IL-6) which augments production of vascular endothelial growth factor (VEGF) from mesothelioma cells. We previously reported the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody. Since NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. In this study, we report VEGF targeting through NRI expression based on adenovirus-mediated gene delivery in mesothelioma cells. We constructed an NRI expression vector in the context of a tropism-modified adenovirus vector that had enhanced infectivity in mesothelioma cells. This virus effectively induced NRI secretion from mesothelioma cells. This virus infection also reduced the VEGF production in mesothelioma cells. These results indicate that NRI shows potential as an agent in the treatment of mesotheliomas.

  7. S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

    DEFF Research Database (Denmark)

    de Nully Brown, P; Jensen, P O; Diamant, M

    1998-01-01

    .0 microg/kg (n = 6) by subcutaneous injection once daily for 5 days and chemotherapy was administered on the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling index (LI) was heterogeneous, but no statistically significant change was noted for this particular group as a whole. In two......, our study demonstrated that rhIL-6 can be administered safely to patients with refractory MM, but the cell cycle recruitment approach was not sufficiently effective to be of clinical value.......The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S...

  8. Correlation between CT grading and blood interleukin-6 in severe acute pancreatitis

    International Nuclear Information System (INIS)

    Yokohari, Kenji; Hirasawa, Hiroyuki; Oda, Shigeto; Shiga, Hidetoshi; Nakanishi, Kazuya; Nakamura, Masataka

    2003-01-01

    Computed tomography (CT) and an evaluating of the degree of severity in patients with severe acute pancreatitis (SAP) are required to decide the therapeutic strategy. We measured blood interleukin-6 (IL-6) in critically ill patients at our intensive care unit (ICU) in a daily clinical setting. To determine the significance of grading CT findings in SAP, we studied the correlation between CT grading and blood IL-6 in SAP patients on ICU admission. Among 31 SAP cases, 66 were CT grade III, 22 CT grade IV, and 3 cases CT grade V. Patients with a higher CT grade tended to have higher blood IL-6. Data also showed that mean blood IL-6 among SAP patients in stage 2 was significantly higher than that among those in stage 3 (p<0.05). From these results, we concluded that CT grading and IL-6 blood level have a different significance in the management of SAP patients. (author)

  9. Metabolic effects of interleukin-6 in human splanchnic and adipose tissue

    DEFF Research Database (Denmark)

    Lyngsø, Dorthe; Simonsen, Lene; Bülow, Jens

    2002-01-01

    Interleukin-6 (IL-6) was infused intravenously for 2.5 h in seven healthy human volunteers at a dose giving rise to a circulating IL-6 concentration of approximately 35 ng l(-1). The metabolic effects of this infusion were studied in subcutaneous adipose tissue on the anterior abdominal wall...... and in the splanchnic tissues by the Fick principle after catheterizations of an artery, a subcutaneous vein draining adipose tissue, and a hepatic vein, and measurements of regional adipose tissue and splanchnic blood flows. In control studies without IL-6 infusion subcutaneous adipose tissue metabolism was studied...... infusion. It is concluded that IL-6 elicits lipolytic effects in human adipose tissue in vivo, and that IL-6 also has effects on the splanchnic lipid and carbohydrate metabolism....

  10. Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships.

    LENUS (Irish Health Repository)

    O'Donovan, Aoife

    2012-02-01

    Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases.

  11. Usefulness of interleukin 6 levels in the cerebrospinal fluid for the diagnosis of bacterial meningitis.

    Science.gov (United States)

    Takahashi, Waka; Nakada, Taka-aki; Abe, Ryuzo; Tanaka, Kumiko; Matsumura, Yosuke; Oda, Shigeto

    2014-08-01

    Interleukin 6 (IL-6) is a proinflammatory cytokine produced during infections. We hypothesized that IL-6 levels in the cerebrospinal fluid (CSF) would be elevated in bacterial meningitis and useful for diagnosing and predicting neurologic outcomes. For the differentiation of bacterial meningitis, serum and CSF samples were obtained from patients with an altered level of consciousness. Patients were classified into 3 groups: bacterial meningitis, nonbacterial central nervous system disease, and other site sepsis. Of the 70 patients included in this study, there were 13 in the bacterial meningitis group, 21 in the nonbacterial central nervous system disease group, and 36 in the other site sepsis group. The CSF IL-6 level was significantly higher in the bacterial meningitis group than in the other 2 groups (Pbacterial meningitis. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Sex Differences in the Association between Level of Childhood Interleukin-6 and Insulin Resistance in Adolescence

    DEFF Research Database (Denmark)

    Bugge, Anna; El-Naaman, Bianca; G McMurray, Robert

    2012-01-01

    The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO(2peak)) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were......-IR at age 13 yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58-8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence...

  13. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J

    1999-01-01

    and reactive astrocytes surrounding the lesion site. In addition, expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and metallothionein-I+II (MT-I+II) were increased in these cells, while the brain-specific MT-III was only moderately upregulated. In IL-6-/- mice, however, the response...... of brain macrophages and reactive astrocytes was markedly depressed and the number of NSE positive neurons was reduced. Brain damage-induced GM-CSF and MT-I+II expression were also markedly depressed compared to IL-6+/+ mice. In contrast, MT-III immunoreactivity was markedly increased in brain macrophages......Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...

  14. Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level

    Directory of Open Access Journals (Sweden)

    Juan E. Losa García

    1999-01-01

    Full Text Available In addition to its well-established effect on T cells, cyclosporin A (CsA also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO. Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a inhibition of the synthesis of an early common regulatory protein, (b inhibition of cytokine gene transcription, or (c modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.

  15. Role of Interleukin-6 in the Radiation Response of Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Miao-Fen, E-mail: miaofen@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Hsieh, Ching-Chuan [College of Medicine, Chang Gung University, Taiwan (China); Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); Chen, Wen-Cheng [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Lai, Chia-Hsuan [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China)

    2012-12-01

    Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6-neutralizing antibody for 24 hours or stably transfected with IL-6-silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6-silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

  16. Enhancing recombinant interleukin-6 production yield by fermentation optimization, two-step denaturing, and one-step purification.

    Science.gov (United States)

    Ahmed, Nadeem; Abbas, Rabbia; Khan, Mohsin Ahmad; Bashir, Hamid; Tahir, Saad; Zafar, Ahmad Usman

    2017-08-22

    Interleukin-6 a pleiotropic cytokine involved in a wide range of biological activities. So the large-scale production of biologically active recombinant human interleukin-6 is important for its structural and functional studies. Here, we report an optimized method for shake flask fermentation and a simplified high-yield purification procedure for the recombinant interleukin-6. This high-yield expression method not only involves the optimization of the fermentation condition but also the single step purification method as well as a two-step denaturing and one-step refolding process. This approach replaces the more conventional procedure of protein solubilization and refolding. Through applying these strategies, the final cell density and overall product yield of the recombinant human interleukin-6 were obtained as 20.4 g as cell biomass and 150 mg as purified active protein from the I-L of the culture. The purified protein was characterized by HPLC and SDS-PAGE. The results of the current work demonstrate that the described method may be used to develop the process for industrial-scale production of the biologically active recombinant interleukin-6 protein. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  17. Interleukin-6 levels in female rats with protamine sulfate-induced chronic cystitis treated with hyaluronic acid.

    Science.gov (United States)

    Lv, Yi-Song; Yao, You-Sheng; Lin, Ming-En; Rong, Lu; Deng, Bi-Hua; Huang, Jian; Hao, Wei-Ping

    2013-10-01

    To measure interleukin-6 levels in a protamine sulfate-induced chronic cystitis rat model treated with hyaluronic acid, and to study the correlation among interleukin-6, bladder inflammatory degree and voiding frequency. A chronic cystitis model was created in female rats by using long-term intermittent intravesical protamine sulfate (0.5 mL, 30 mg/mL). Then, hyaluronic acid (0.5 mL, 0.8 mg/mL) was also instilled intravesically in the rats. Interleukin-6 levels were analyzed with immunohistochemistry, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was carried out to examine bladder inflammatory degree based on a four-point scoring system (from 0 - none to 3 - severe). Voiding patterns were investigated by cystometrography. According to cystometrography, protamine sulfate-induced rats had significantly shorter intercontraction intervals and less bladder capacity (P hyaluronic acid, both intercontraction intervals and bladder capacity increased significantly (P hyaluronic acid decreases interleukin-6 levels, as well as the severity of bladder inflammation and voiding frequency in a rat model of chronic cystitis. Interleukin-6 levels closely correlate with the inflammatory degree and voiding frequency. Thus, they can be regarded as an assessment measure of therapeutic impact. © 2013 The Japanese Urological Association.

  18. Evaluation of BCL-2 and transforming growth factor alpha ...

    African Journals Online (AJOL)

    Evaluation of BCL-2 and transforming growth factor alpha oncoproteins in patients with chronic hepatitis C infection: impact on hepatocellular carcinoma. Mahmoud I Hassan, Amal Abou El Fadle, Gamal M Kenawy, Fayda I Abdel Motaleb, Fatma M AbdelSalam ...

  19. A Study of Inflammatory/Necrosis Biomarkers in the Fracture of the Femur Treated with Proximal Femoral Nail Antirotation

    Directory of Open Access Journals (Sweden)

    Mariapaola Marino

    2015-01-01

    Full Text Available Pertrochanteric fractures are common injuries in adults and source of morbidity and mortality among the elderly. Different surgical techniques were recommended for their treatment but undoubtedly they add an additional inflammatory trauma along the fracture itself. Many attempts to quantify the degree of approach-related trauma are carried out through measurements of systemic inflammatory parameters. In this study we prospectively analyzed laboratory data of 20 patients over eighty with pertrochanteric fracture of the femur treated with proximal femoral nail antirotation (PFNA. This is an excellent device for osteosynthesis because it can be easily and quickly inserted by a mini-incision providing stable fixation and early full mobilization. Serum tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, C-reactive protein (CRP, and plasma creatin kinase (CK were evaluated 1 hour preoperatively and 24 hours postoperatively. Our results show that PFNA did not induce significant increments in serum levels of inflammatory cytokines TNF-α and IL-6; CRP was elevated preoperatively in correlation with waiting time for surgery; CRP and CK showed a significant increment in the first postoperatory day; CK increment was correlated with surgical time length. We conclude that, for the markers we analyzed, PFNA shows a low biomechanical-inflammatory profile that represents an advantage over other techniques.

  20. Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

    Science.gov (United States)

    Hahn, Ulrich

    2017-12-06

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  1. Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells.

    Science.gov (United States)

    Ogawa, Hiroyuki; Koyanagi-Aoi, Michiyo; Otani, Kyoko; Zen, Yoh; Maniwa, Yoshimasa; Aoi, Takashi

    2017-09-26

    In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named them "lung cancer organoids". We found that interleukin-6 (IL-6), which was expressed in the lung induced CSCs, facilitates the formation of lung cancer organoids via the conversion of mesenchymal stem cells into alpha-smooth muscle actin (αSMA)-positive cells. Interestingly, the combination of anti-IL-6 antibody and cisplatin could destroy the lung cancer organoids, while cisplatin alone could not. Furthermore, IL-6 mRNA-positive cancer cells were found in clinical lung cancer samples. These results suggest that IL-6 could be a novel therapeutic target in lung cancer.

  2. EFFECT OF TWO TAPERING METHODS ON INTERLEUKIN-6, CORTISOL AND PERFORMANCE IN ELITE MALE WRESTLER

    Directory of Open Access Journals (Sweden)

    A.B. Mehranpour

    2015-08-01

    Full Text Available Purpose : This study examined that effect of two types of tapering on interleukin-6(IL-6, cortisol and performance in elite male wrestler. Material : After 4 weeks of progressive training, wrestlers were randomly divided into three equal groups, 1-control group (N=10 continued performing progressive training for one week, 2-taper group 1 (N=10 continued with a 50% reduction in training volume for one week, 3-taper group 2 (N=10 continued with a 75% reduction in volume of training for one week .plasma blood IL-6 and cortisol levels were assayed from analysis obtained via standard ELISA. Also general strength of muscles was recorded as a performance test. All data were collected before and after progressive training and also after one week of tapering period. Results : There were significant reduction of IL-6 and cortisol levels in both tapering group comparing with control group (P≤0.05.There was significant reduction of IL-6 and cortisol levels among tapering 50% and tapering 75% after tapering period (P≤0.05. Also there was significant increase of general strength of muscles between tapering 75% and control group (P≤0.05. Conclusion : hence, one week tapering with 75% reduction in training volume after progressive training while the intensity kept high is effective strategy for reduction of IL-6, and cortisol levels and also increase performance. It seems that higher reduction of training volume when the intensity kept high is a good strategy for wrestler before main competition.

  3. Chemerin and interleukin-6 levels in obese individuals following periodontal treatment.

    Science.gov (United States)

    Balli, U; Ongoz Dede, F; Bozkurt Dogan, S; Gulsoy, Z; Sertoglu, E

    2016-10-01

    To investigate changes in the levels of gingival crevicular fluid (GCF) chemerin and interleukin-6 (IL-6) in both obese/non-obese individuals with periodontitis following non-surgical periodontal therapy. Individuals (n = 80) were split into four groupings according to periodontal/anthropometric parameters: (i) periodontal healthy without obesity; (ii) chronic periodontitis (CP) without obesity; (iii) periodontal healthy with obesity; and (iv) CP with obesity. Individuals with periodontitis were treated with non-surgical periodontal therapy. Both GCF sampling procedures and clinical periodontal measures were performed prior to treatment and 6 weeks thereafter. Enzyme-linked immunosorbent assay was utilized to measure both chemerin and IL-6 levels. Greater values for chemerin and IL-6 were observed in obese individuals compared to their non-obese controls and in individuals with CP compared to their periodontal healthy controls (P obese groups (P integral part in the pathologic mechanisms that relate adipokines to both periodontal disease and obesity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Salivary Interleukin-6 - A pioneering marker for correlating diabetes and chronic periodontitis: A comparative study

    Directory of Open Access Journals (Sweden)

    Anitha Balaji

    2017-01-01

    Full Text Available Background: Periodontitis is a chronic inflammatory disease which is multifactorial. Diabetes mellitus (DM is one of the major systemic factors to influence the severity of chronic periodontitis. Numerous inflammatory markers are produced in the course of the disease which is secreted in saliva too. This study evaluates the salivary concentrations of interleukin-6 (IL-6 in periodontitis patients with type 2 diabetes. Materials and Methods: Whole saliva samples were collected from eighty patients who were further divided into four groups; healthy (control group; n = 20, untreated periodontitis (UPD; n = 20, DM (DM; n = 20, and UPD + DM (n = 20 groups. Salivary IL-6 concentrations were determined by standard enzyme-linked immunosorbent assay. Results: Results show that the UPD patients with and without DM exhibited higher concentrations of salivary IL-6 than the control group and diabetes groups. Further, the salivary IL-6 was correlated with glycosylated hemoglobin A levels in patients with diabetes. Conclusion: Concentration of salivary IL-6 was elevated in patients with periodontitis with and without diabetes. Thus, salivary IL–6 levels can be considered as an important biomarker in the diagnosis of periodontitis and diabetes.

  5. miR-217 suppresses proliferation and promotes apoptosis in cardiac myxoma by targeting Interleukin-6.

    Science.gov (United States)

    Zhang, Jing; Wang, Cui; Xu, Huimin

    2017-08-26

    Cardiac myxoma (CM) is a prevalent primary cardiac tumor. miR-217 plays a vital role in tumorigenesis of various cancers, however, its role and underlying molecular mechanism in human CM remain poorly understood. Here, we reported that the expression of miR-217 was downregulated in CM tissues and inversely correlated with the expression of Interleukin-6 (IL-6) mRNA. Gain-of-function analysis indicated that overexpression of miR-217 inhibited the proliferation and promoted the apoptosis of the primary CM cells. Bioinformatics analysis showed that IL-6 was a direct target gene of miR-217, which is confirmed by the dual luciferase assays. Moreover, downregulation of IL-6 by small interference RNA (siRNA) mimicked the tumor-suppressive effects of miR-217 in CM. Furthermore, rescue experiments pointed out that restoration of IL-6 expression abrogated the anti-proliferative and pro-apoptotic effect induced by miR-217 overexpression in CM cells. Taken together, we validated that miR-217 could act as a tumor suppressor in CM by directly targeting 3'UTR of IL-6 gene, indicating that manipulation of miR-217 may be a potential therapeutic strategy for CM patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Role of interleukin-6 levels in cardiovascular autonomic dysfunction in type 2 diabetic patients

    International Nuclear Information System (INIS)

    Shinohara, Tetsuji; Takahashi, Naohiko; Kakuma, Tetsuya; Hara, Masahide; Yoshimatsu, Hironobu; Yufu, Kunio; Anan, Futoshi; Nakagawa, Mikiko; Saikawa, Tetsunori

    2008-01-01

    Increased serum interleukin-6 (IL-6) levels are associated with an increased risk of cardiovascular disease, and cardiovascular autonomic dysfunction is associated with high mortality in type 2 diabetic patients. However, the relationship between IL-6 levels and cardiovascular autonomic dysfunction has not been fully elucidated. The aim of this study was to determine whether serum IL-6 levels are associated with cardiovascular autonomic dysfunction in type 2 diabetic patients. Eighty type 2 diabetic patients who did not have organic heart disease were categorized into a high IL-6 group (>2.5 pg/ml, n= 0, age 59±12 years) or a non-high IL-6 group ( 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. The body mass index values (BMI), fasting insulin levels and homeostasis model assessment index values were higher in the high IL-6 group than in the non-high IL-6 group (p 123 I-MIBG myocardial uptake values were lower (p 123 I-MIBG was higher (p 123 I-MIBG during the delayed phase. The results indicate that elevated IL-6 levels are associated with depressed cardiovascular autonomic function and obesity in type 2 diabetic patients. (orig.)

  7. Interleukin-6 deficiency attenuates angiotensin II-induced cardiac pathogenesis with increased myocyte hypertrophy.

    Science.gov (United States)

    Chen, Fan; Chen, Dandan; Zhang, Yubin; Jin, Liang; Zhang, Han; Wan, Miyang; Pan, Tianshu; Wang, Xiaochuan; Su, Yuheng; Xu, Yitao; Ye, Junmei

    2017-12-16

    Interleukin-6 (IL-6) signaling is critical for cardiomyocyte hypertrophy, while the role of IL-6 in the pathogenesis of myocardium hypertrophy remains controversial. To determine the essential role of IL-6 signaling for the cardiac development during AngII-induced hypertension, and to elucidate the mechanisms, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were infused subcutaneously with either vehicle or AngII (1.5 μg/h/mouse) for 1 week. Immunohistological and serum studies revealed that the extents of cardiac fibrosis, inflammation and apoptosis were reduced in IL-6 KO heart during AngII-stimulation, while cardiac hypertrophy was obviously induced. To investigate the underlying mechanisms, by using myocardial tissue and neonatal cardiomyocytes, we observed that IL-6/STAT3 signaling was activated under the stimulation of AngII both in vivo and in vitro. Further investigation suggested that STAT3 activation enhances the inhibitory effect of EndoG on MEF2A and hampers cardiomyocyte hypertrophy. Our study is the first to show the important role of IL-6 in regulating cardiac pathogenesis via inflammation and apoptosis during AngII-induced hypertension. We also provide a novel link between IL-6/STAT3 and EndoG/MEF2A pathway that affects cardiac hypertrophy during AngII stimulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ulrich Hahn

    2017-12-01

    Full Text Available Interleukin-6 (IL-6 is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT. Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  9. Effects of lipopolysaccharide and interleukin-6 on cataleptic immobility and locomotor activity in mice.

    Science.gov (United States)

    Bazovkina, Daria V; Tibeikina, Marina A; Kulikov, Alexander V; Popova, Nina K

    2011-01-10

    Catalepsy (animal hypnosis, tonic immobility) is a type of passive defensive behavior. Its exaggerated form is a syndrome of some psychopathological disorders. Numerous neurotransmitters have impact on the regulation of catalepsy. In this paper we demonstrated the involvement of interleukin-6 (IL-6) in the mechanism of cataleptic immobility. Effects of exogenous IL-6 treatment (7.5 and 10μg/kg, i.p) or stimulation of endogenous IL-6 secretion with lipopolysaccharide (LPS) administration (50, 100 and 200μg/kg, i.p.) on catalepsy and locomotor activity were studied in adult C57BL/6 male mice. IL-6 induced catalepsy in 70% (7.5μg/kg) or 72.7% (10μg/kg) of animals with no effect on locomotor activity. LPS administration reduced distance travelled and number of rears in the open field at any dose used, however, only high doses (100 or 200μg/kg) of the toxin induced catalepsy in 50% of mice. This result indicates that IL-6 is involved in the regulation of catalepsy, this effect is specific and does not arise from inhibition of locomotor activity. The study provides a new evidence on participation of IL-6 in mechanisms of abnormal behavior. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Effect of Periodontal Therapy on Crevicular Fluid Interleukin-6 and Interleukin-8 Levels in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Paschalina Goutoudi

    2012-01-01

    Full Text Available Purpose. The aim of this study was to analyse the levels of interleukin-6 (IL-6 and interleukin-8 (IL-8 in gingival crevicular fluid (GCF of patients with chronic periodontitis prior to and following surgical and/or nonsurgical periodontal therapy for a period of 32 weeks. Methods. GCF samples were obtained from 24 nondiseased and 72 diseased sites of 12 periodontal patients prior to as well as at 6, 16, and 32 weeks following non-surgical and surgical periodontal therapy. IL-6 and IL-8 levels were determined by enzyme-linked immunosorbent assay (ELISA. Results. Periodontal treatment improved all clinical parameters. Both treatment modalities resulted in similar IL-6 as well as IL-8 levels. Mean IL-6 and IL-8 concentrations were significantly higher in non-diseased compared to diseased sites and increased significantly following treatment in diseased sites. Mean total amounts of IL-6 and IL-8 (TAIL-6, TAIL-8 did not differ significantly between diseased and nondiseased sites, while following therapy TAIL-8 levels decreased significantly. Conclusions. The data suggest that periodontal therapy reduced the levels of IL-8 in GCF. However, a strong relationship between IL-6, IL-8 amounts in GCF and periodontal destruction and inflammation was not found.

  11. Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Shiga

    2016-01-01

    Full Text Available Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6 in colorectal cancer (CRC. Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS and disease-free survival (DFS rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

  12. Interleukin 6 variable number of tandem repeats (VNTR) gene polymorphism in centenarians.

    Science.gov (United States)

    Capurso, C; Solfrizzi, V; D'Introno, A; Colacicco, A M; Capurso, S A; Semeraro, C; Capurso, A; Panza, F

    2007-11-01

    Recent population-based studies identified the magnitude of interleukin 6 (IL6) serum levels as a marker for functional disability, and a predictor of disability and mortality among the elderly. We investigated whether there was evidence in Southern Italy of an association between the IL6 gene variable number of tandem repeats (VNTR) polymorphism and extreme longevity, and tested for the possible interaction of apolipoprotein E (APOE) alleles with the IL6 VNTR alleles. Four alleles coding for variants of four different lengths have been identified: allele A [760 base pairs (bp)], allele B (680 bp), allele C (640 bp), and allele D (610 bp). IL6 VNTR and APOE allele and genotype frequencies were studied in a total of 61 centenarians and 94 middle-aged subjects from Southern Italy. The IL6 VNTR allele B was overrepresented in the younger control group compared with centenarians (odds ratio: 0.56, 95% confidence interval: 0.35-0.88, Bonferroni p-value VNTR alleles and APOE alleles on the odds ratios to reach extreme longevity were evaluated for the smallest number of subjects in centenarians and younger controls. Our findings suggested that the presence of the IL6 VNTR allele B could be detrimental for reaching extreme longevity.

  13. Negative Emotions Predict Elevated Interleukin-6 in the United States but not in Japan

    Science.gov (United States)

    Miyamoto, Yuri; Boylan, Jennifer Morozink; Coe, Christopher L.; Curhan, Katherine B.; Levine, Cynthia S.; Markus, Hazel Rose; Park, Jiyoung; Kitayama, Shinobu; Kawakami, Norito; Karasawa, Mayumi; Love, Gayle D.; Ryff, Carol D.

    2013-01-01

    Previous studies conducted in Western cultures have shown that negative emotions predict higher levels of pro-inflammatory biomarkers, specifically interleukin-6 (IL-6). This link between negative emotions and IL-6 may be specific to Western cultures where negative emotions are perceived to be problematic and thus may not extend to Eastern cultures where negative emotions are seen as acceptable and normal. Using samples of 1044 American and 382 Japanese middle-aged and older adults, we investigated whether the relationship between negative emotions and IL-6 varies by cultural context. Negative emotions predicted higher IL-6 among American adults, whereas no association was evident among Japanese adults. Furthermore, the interaction between culture and negative emotions remained even after controlling for demographic variables, psychological factors (positive emotions, neuroticism, extraversion), health behaviors (smoking status, alcohol consumption), and health status (chronic conditions, BMI). These findings highlight the role of cultural context in shaping how negative emotions affect inflammatory physiology and underscore the importance of cultural ideas and practices relevant to negative emotions for understanding of the interplay between psychology, physiology, and health. PMID:23911591

  14. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6

    International Nuclear Information System (INIS)

    Miles, S.A.; Rezai, A.R.; Salazar-Gonzalez, J.F.; Meyden, M.V.; Stevens, R.H.; Mitsuyasu, R.T.; Martinez-Maza, O.; Logan, D.M.; Taga, Tetsuya; Hirano, Toshio; Kishimoto, Tadamitsu

    1990-01-01

    Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1β, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, the authors examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. The authors found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [ 3 H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at >10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells

  15. Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

    Directory of Open Access Journals (Sweden)

    Sven Kruspe

    2014-01-01

    Full Text Available Photodynamic therapy (PDT uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6 with a human interleukin-6 receptor (IL-6R binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+ cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

  16. Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites

    DEFF Research Database (Denmark)

    Hamid, Yasmin H; Urhammer, Søren A; Jensen, Dorit P

    2004-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130......). The IL6R gene maps to an important candidate locus for type 2 diabetes on chromosome 1q21. An Asp358Ala polymorphism of the IL6R has been reported to associate with obesity in Pima Indians. We investigated the Asp358Ala polymorphism in relation to type 2 diabetes, obesity, and other pre-diabetic...... quantitative traits among Danish whites. By applying a recessive genetic model in a case-control study of 1,349 type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a significant difference in genotype distribution (P = 0.008) and in allele frequency (Ala-allele 38.3% [95% CI 36...

  17. Interleukin-6 release is higher across arm than leg muscles during whole-body exercise

    DEFF Research Database (Denmark)

    Helge, Jørn W; Klein, Ditte K; Andersen, Thor Munch

    2011-01-01

    ± 7 and 47 ± 7 µmol min(-1) (kg lean limb mass)(-1)) were lower, glucose uptake similar (51 ± 12 and 41 ± 8 mmol min(-1) (kg lean limb mass)(-1)) and lactate release higher (82 ± 32 and -2 ± 12 µmol min(-1) (kg lean limb mass)(-1)) in arms than legs, respectively, during exercise (P ....05). No correlations were present between IL-6 release and exogenous substrate uptakes. Muscle glycogen was similar in arms and legs before exercise (388 ± 22 and 428 ± 25 mmol (kg dry weight)(-1)), but after exercise it was only significantly lower in the leg (219 ± 29 mmol (kg dry weight)(-1)). The novel finding......Exercising muscle releases interleukin-6 (IL-6), but the mechanisms controlling this process are poorly understood. This study was performed to test the hypothesis that the IL-6 release differs in arm and leg muscle during whole-body exercise, owing to differences in muscle metabolism. Sixteen...

  18. Socioeconomic and Psychosocial Predictors of Interleukin-6 in the MIDUS National Sample

    Science.gov (United States)

    Morozink, Jennifer A.; Friedman, Elliot M.; Coe, Christopher L.; Ryff, Carol D.

    2010-01-01

    Objective To investigate whether psychosocial factors (i.e., depression, anxiety, and well-being) moderate educational gradients in interleukin-6 (IL-6) levels using data from the Survey of Mid-life Development in the U.S. (MIDUS). The influences of educational attainment and psychosocial factors on IL-6 in middle aged and older adults were also examined. Design Telephone interviews and mail surveys were utilized to collect educational attainment and psychosocial information from participants (N = 1028). Respondents also participated in an overnight clinic visit, during which health information and a fasting blood sample was obtained. Main Outcome Measures Serum levels of IL-6. Results . Greater educational attainment predicted lower levels of IL-6 independent of age and gender, although this effect was attenuated after taking health behaviors, body mass index, waist-to-hip ratio, and chronic illnesses into account. Psychological well-being interacted with education to predict IL-6, such that for those with less education, higher well-being was associated with lower levels of IL-6. Conclusion The findings indicate a strong association between education and inflammation, which can be further moderated by psychosocial factors. The health benefits associated with psychological well-being were particularly evident for individuals with low educational attainment. PMID:20954777

  19. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes

    DEFF Research Database (Denmark)

    Fosgerau, K; Galle, P; Hansen, T

    2010-01-01

    Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct...... role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5% in the type 2 diabetic patients and 1% in the controls (odds ratio 2.5, 95% confidence interval 1.2-4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6...... were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056+/-62 vs 1793+/-62, P=0.05) as compared with sham-vaccinated mice, when...

  20. Maternal serum interleukin-6 in the management of patients with preterm premature rupture of membranes.

    Science.gov (United States)

    Sayed Ahmed, Waleed Ali; Ahmed, Magdy Refaat; Mohamed, Mariam Lotfi; Hamdy, Mostafa Ahmed; Kamel, Zenab; Elnahas, Khaled Mohamed

    2016-10-01

    To evaluate the clinical usefulness of maternal serum interleukin-6 for the detection of subclinical chorioamnionitis and in the prediction of the latency period in patients with preterm premature rupture of membrane (PPROM). The study group included 60 patients at 24-34 weeks of gestation complaining of PPROM. Laboratory investigations included serial measurements of IL-6, TLC and CRP. Conservative management was carried out till 36 weeks unless delivery was indicated beforehand. The main outcome measures were the latency period and the occurrence of subclinical chorioamnionitis. The mean gestational age at presentation was 30.9 weeks and 35.2 weeks at delivery. The mean IL-6 level at presentation was 4.7 pg/ml. There was no correlation between IL-6 at presentation and the latency period. In addition, those diagnosed as having subclinical chorioamnionitis by placental histopathology had significantly higher levels of IL-6 at delivery. Taking IL-6 level cutoff point of 8.5 pg/ml, histological chorioamnionitis, RDS and NICU admission were significantly higher above that level while neonatal birth weight, Apgar scores at one and five minutes were significantly lower. Maternal serum IL-6 at the time of PPROM has no correlation to the latency period while IL-6 levels at the time of delivery have significant correlation to the subclinical chorioamnionitis and neonatal outcome measures.

  1. Association of Klotho and interleukin 6 gene polymorphisms with aging in Han Chinese population.

    Science.gov (United States)

    Zhang, W-G; Bai, X-J; Chen, D-P; Lv, Y; Sun, X-F; Cai, G-Y; Bai, X-Y; Chen, X-M

    2014-12-01

    Certain gene polymorphisms are associated with human aging. This study investigated polymorphisms of a metabolism-related gene, Klotho, and an inflammatory gene, IL6, for association with the aging process in a healthy Han Chinese population. A total of 482 healthy subjects were recruited and divided into aging and young groups according to chronological age and biological age. Snapshots were used to detect a Klotho gene tag SNP (rs571118) and the F-SNPs rs9536314 (F352V) and rs9527025 (C370S), and an interleukin 6 (IL-6) gene tag SNP (rs1524107) and the F-SNPs rs1800795 (-174G/C) and rs1800796 (-572G/C). Klotho F352V and IL-6-174G/C was G homozygous, C370S was T homozygous while IL-6-572G/C MAF less than 5%. There was a statistically significant difference in the Klotho rs571118 SNP between chronological age groups, but not biological age groups. However, other SNPs, including IL-6 gene SNPs, didn't correlate with age in the Han Chinese population. Human aging is a complex process that includes chronological and biological aging. Our current data showed that Klotho gene rs571118 SNP was associated with chronological aging, but not biological aging, in a Han Chinese population. Further study will investigate genetic build up for the difference between chronological and biological aging.

  2. Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer.

    Science.gov (United States)

    Han, Jun; Meng, Qingyang; Xi, Qiulei; Zhang, Yongxian; Zhuang, Qiulin; Han, Yusong; Jiang, Yi; Ding, Qiurong; Wu, Guohao

    2016-01-01

    Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

  3. Immunoexpression of interleukin-6 in drug-induced gingival overgrowth patients

    Directory of Open Access Journals (Sweden)

    P R Ganesh

    2016-01-01

    Full Text Available Background: To analyze the role of proinflammatory cytokines in drug-induced gingival enlargement in Indian population. Aim: To evaluate for the presence of interleukin-6 (IL-6 in drug-induced gingival enlargement and to compare it with healthy control in the absence of enlargement. Materials and Methods: Thirty-five patients selected for the study and divided into control group (10 and study group (25 consisting of phenytoin (10; cyclosporin (10 and nifedipine (5 induced gingival enlargement. Gingival overgrowth index of Seymour was used to assess overgrowth and allot groups. Under LA, incisional biopsy done, tissue sample fixed in 10% formalin and immunohistochemically evaluated for the presence of IL-6 using LAB-SA method, Labeled- Streptavidin-Biotin Method (LAB-SA kit from Zymed- 2nd generation LAB-SA detection system, Zymed Laboratories, CA. The results of immunohistochemistry were statistically analyzed using Kruskaal–Wallis and Mann–Whitney test. Results: The data obtained from immunohistochemistry assessment shows that drug-induced gingival overgrowth (DIGO samples express more IL-6 than control group and cyclosporin expresses more IL-6 followed by phenytoin and nifedipine. Conclusion: Increased IL-6 expression was noticed in all three DIGO groups in comparison with control group. Among the study group, cyclosporin expressed maximum IL-6 expression followed by phenytoin and nifedipine.

  4. Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery.

    Science.gov (United States)

    Hoppe, Michael; Lönnerdal, Bo; Hossain, Bakhtiar; Olsson, Sigvard; Nilsson, Folke; Lundberg, Per-Arne; Rödjer, Stig; Hulthén, Lena

    2009-01-01

    Anemia of inflammation in patients with acute or chronic acute-phase activation is a common clinical problem. Hepcidin is a peptide shown to be the principal regulator of the absorption and systemic distribution of iron. Main inducers of hepcidin are iron overload, hypoxia and inflammation, where the latter has been linked to hepcidin via increased interleukin-6 (IL-6). This article addresses the impact and time course of postoperative acute-phase reaction in humans following heart surgery on prohepcidin, hepcidin, hematological markers and IL-6 concentrations. Serum concentrations of prohepcidin, hepcidin, IL-6 and hematological iron parameters were studied in five male patients without infection before and after heart surgery. This study, which is the first to report the impact on serum hepcidin and serum prohepcidin concentrations in patients following surgery, clearly demonstrates the induction of hypoferremia due to the postoperative acute-phase reaction. Significant changes were seen for serum iron concentration, transferrin saturation, total iron binding capacity and hemoglobin concentration. A significant increase in ferritin concentration was seen 96-144 h postoperatively. Additionally, there were significant alterations in both serum hepcidin after 96-144 h and serum prohepcidin after 48 h compared with preoperative values. Serum prohepcidin decreased, whereas serum hepcidin increased. In conclusion, changes in serum prohepcidin were followed by an increase in serum hepcidin. This speaks in favor of a chain of action where proteolytic trimming of serum prohepcidin results in increased serum hepcidin. However, hypoferremia appeared prior to the changes in serum prohepcidin and serum hepcidin.

  5. Sex Differences in the Association between Level of Childhood Interleukin-6 and Insulin Resistance in Adolescence

    Directory of Open Access Journals (Sweden)

    Anna Bugge

    2012-01-01

    Full Text Available The purpose of this study was to determine whether levels of interleukin-6 (IL-6 in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO2peak moderate this relationship. Methods. 292 nine-year-old children (n=292 were followed for 4 years. Anthropometrics and VO2peak were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r=0.223, P=0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58–8.57 being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls.

  6. Sex Differences in the Association between Level of Childhood Interleukin-6 and Insulin Resistance in Adolescence

    Science.gov (United States)

    Bugge, Anna; El-Naaman, Bianca; G. McMurray, Robert; Froberg, Karsten; Nielsen, Claus Henrik; Müller, Klaus; Andersen, Lars Bo

    2012-01-01

    The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO2peak) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were followed for 4 years. Anthropometrics and VO2peak were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR) was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58–8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls. PMID:22272193

  7. Prenatal expression of interleukin 1beta and interleukin 6 in the rat pituitary gland.

    Science.gov (United States)

    Moro, J A; Carretero, J; Alonso, M I; Martín, C; Gato, A; Mano, A de la

    2008-12-01

    It is known that interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) are expressed post-natally in normal and tumoral cells in the anterior pituitary, and that they play a role in both the liberation of different hormones and in the growth, proliferation and tumor formation of the pituitary gland. However, their expression and role during embryonic and fetal development remain unknown. We have performed an immunocytochemistry study of prenatal expression and distribution of IL-1beta and IL-6 in isolated embryonic rat Rathke's pouch prior to birth, more specifically between 13.5 and 19.5 days p.c. Western-blot analysis carried out on 19.5-day p.c. embryos showed positive immunolabelling for IL-1beta and IL-6. These interleukins were initially expressed simultaneously in the rostral and ventral portions of Rathke's pouch in 15.5-day p.c. embryos, and this expression progressed caudodorsally in later developmental stages, extending to most of the hypophysis before birth. The number of cells expressing these interleukins increased throughout this period: 48.22% of anterior pituitary cells expressed IL-6 in 19.5-day embryos, whilst IL-1beta was positive in 39.8% of the cells. Moreover, we have demonstrated that some adenohypophyseal cells co-express both interleukins. Such findings represent the first step towards an understanding of the physiological role of these interleukins in anterior pituitary development.

  8. Simvastatin prevents the induction of interleukin-6 gene expression by titanium particles in human osteoblastic cells.

    Science.gov (United States)

    Vallés, Gema; Pérez, Concepción; Boré, Alba; Martín-Saavedra, Francisco; Saldaña, Laura; Vilaboa, Nuria

    2013-01-01

    One of the most important complications of total joint arthroplasty is failure associated with periprosthetic osteolysis, a process mainly initiated by the biological response to wear-derived products from the biomaterials in service. The inflammatory mediator interleukin-6 (IL-6) plays a key role in the establishment and progression of aseptic loosening. Metal particles specifically up-regulate IL-6 production in bone-forming cells and implant-bone interfacial tissues. The use of statins has been recently associated with a significantly reduced risk of revision in patients that undergo total hip arthroplasty. We hypothesized that simvastatin (Simv) could modulate the osteoblastic response to titanium particles (Ti) by attenuating the production of IL-6. Pre-treatment of human osteoblastic cells with Simv down-regulated Ti particle-induced IL-6 gene expression at mRNA and protein levels. The effect of Simv on Ti-induced IL-6 production in osteoblastic cells could not be explained by inhibition of the internalization of metal particles. The mechanism involved in this down-regulation is based in the inhibition of the HMG-CoA/GGPP/RhoA/ROCK pathway, independently of Simv effects in the cholesterol synthesis. The cytokine-lowering property of Simv has been observed in Saos-2 cells and human primary osteoblasts (hOBs) exposed to Ti particles, and was further enhanced when hOBs were co-cultured with macrophages. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Serum Interleukin-6 Expression Level and Its Clinical Significance in Patients with Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Min Yang

    2013-01-01

    Full Text Available Objective. To analyze serum interleukin-6 (IL-6 expression level and its clinical significance in patients with dermatomyositis. Methods. Blood samples from 23 adult patients with dermatomyositis (DM, 22 with systemic lupus erythematosus (SLE, 22 with rheumatoid arthritis (RA, 16 with Sjögren's syndrome (SS, and 20 healthy controls were collected. The IL-6 concentration was detected by chemiluminescence immunoassay. Correlations between IL-6 expression levels and clinical features or laboratory findings in patients with DM were investigated. Results. IL-6 expression level of DM patients was significantly higher than that of normal controls, significantly lower than that of RA patients, and slightly lower than that of SLE or SS patients with no significant differences. The incidence of fever was significantly higher in the IL-6 elevated group. Serum ferritin (SF and C-reactive protein (CRP were positively correlated with IL-6. Conclusions. IL-6 plays a less important role in DM than in RA. IL-6 monoclonal antibodies may have poor effect in patients with DM.

  10. Activation of the interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma of the parotid gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; Therkildsen, Marianne Hamilton; Grauslund, Morten

    2015-01-01

    The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is of crucial importance in promoting tumorigenesis in several malignant tumors but may also be active in benign tumors, e.g., of pleomorphic adenoma (PA). In this study we characterize ...

  11. The effects of grain-induced subactue ruminal acidosis on interleukin-6 and acute phase response in dairy cows

    DEFF Research Database (Denmark)

    Li, Shucong; Danscher, Anne Mette; Andersen, Pia Haubro

    2014-01-01

    Subacute ruminal acidosis (SARA) resulting from excessive grain feeding to dairy cows is accompanied by an acute phase response. Interleukin 6 (IL-6) has been proposed as a mediator of this response. We tested if the acute phase response associated with grain-induced SARA is mediated by IL-6. Six...

  12. Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Camats, Jordi; Hadberg, Hanne

    2003-01-01

    6-aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes mainly in the brainstem. We have examined the role of interleukin-6 (IL-6) in this degenerative process by using transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice). This s...

  13. Interindividual variation in the response by fibrinogen, C-reactive protein and interleukin-6 to yellow fever vaccination

    NARCIS (Netherlands)

    Verschuur, M.; Beek, M.T. van der; Tak, H.S.; Visser, L.G.; Maat, M.P.M. de

    2004-01-01

    The acute phase reaction is important in many disease processes. Habitual levels of the acute phase proteins fibrinogen, C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with an increased risk of cardiovascular disease, but the dynamic variation of plasma levels of acute phase

  14. Serum Levels of Visfatin and Interleukin-6 in Non-Obese Versus Obese Men with Coronary Artery Disease

    International Nuclear Information System (INIS)

    Naz, S.; Sandhu, Q. S.; Akhtar, A.; Zafar, U.; Khalid, A.; Saeed, M.

    2017-01-01

    Objective: To evaluate and compare the serum levels of visfatin, interleukin-6 and lipid profile in non-obese and obese male patients with coronary artery disease. Study Design: Observational, comparative study. Place and Duration of Study: Punjab Institute of Cardiology and Lahore General Hospital, Lahore, from July to December 2013. Methodology: The participants included 20 non-obese group I with coronary artery disease (CAD) and 20 obese males group II with coronary artery disease (angiographically confirmed). All the participants were in the age group of 35 - 55 years being non-smokers and non-diabetic. Serum visfatin and interleukin-6 levels were analysed by Enzyme Linked Immunosorbent Assay (ELISA). Lipid profile was also evaluated. Results were compared with T-test and Mann Whitney U test. The values were considered significant at 0.05 level of significance. Results: Serum visfatin 9.05 versus 3.9 ng/ml and interleukin-6 12.80 versus 0.60 pg/ml levels were significantly (p-value < 0.001 of both) raised in the obese CAD group as compared to non-obese with CAD. Lipid profile also showed raised levels of total serum cholesterol, low density lipoproteins, triglycerides, very low density lipoproteins and low levels of high density lipoproteins in obese group. Conclusion: Significantly raised levels of serum visfatin and interleukin-6 indicate adipose tissue as an imperative source of these adipocytokines involved in inflammation in CAD. Altered lipid profile also seen in obese patients with CAD. (author)

  15. Interleukin-6 concentrations in the serum of patients with AIDS-associated Kaposi's sarcoma during treatment with interferon-alpha

    NARCIS (Netherlands)

    de Wit, R.; Raasveld, M. H.; ten Berge, R. J.; van der Wouw, P. A.; Bakker, P. J.; Veenhof, C. H.

    1991-01-01

    Interleukin-6 (IL-6) levels were determined in the serum of 14 HIV-1-infected patients with Kaposi's sarcoma, 10 HIV-1-infected patients without symptoms, and 10 healthy male subjects. IL-6 levels were also determined in the serum of the 14 patients with Kaposi's sarcoma during treatment with

  16. The role of tumor necrosis factor alpha in differentiation between malignant and non malignant pleural effusion

    Directory of Open Access Journals (Sweden)

    Heba M. Atef

    2016-07-01

    Conclusion: Pleural fluid level of TNF-α can be used in differentiating malignant from non malignant effusion. Also levels of TNF-α in the serum and pleural fluid could be useful as a complementary marker in the differential diagnosis of two most common types of exudates (tuberculous and malignant.

  17. Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Mohamad Saekhu

    2016-07-01

    Full Text Available Background: The outcome of patients with spontaneous supratentorial intracerebral hemorrhage (SSICH is unsatisfactory. Inflammatory response secondary to brain injury as well as those resulted from surgical procedure were considered responsible of this outcome. This study was intended to elucidate the anti-inflammatory activity of tigecycline by measuring TNF-α level and its neuroprotective effect as represented by inhospital mortality rate.Methods: Patients with SSICH who were prepared for hematoma evacuation were randomized to receive either tigecycline (n=35 or fosfomycine (n=37 as prophylactic antibiotic. TNF-α level was measured in all subjects before surgery and postoperatively on day-1 and day-7. A repeated brain CT Scan was performed on postoperative day-7. The Glasgow outcome scale (GOS and length of stay (LOS were recorded at the time of hospital discharge. Data were analyzed using Mann-Whitney and Chi square test. Relative clinical effectiveness was measured by calculating the number needed to treat (NNT.Results: There was a significant difference regarding the proportion of subject who had  reduced TNF-α level on postoperative day-7 between the groups receiving tigecycline and fosfomycine (62% vs 29%, p=0.022. Decrease brain edema on CT control (86% vs 80%, p=0.580. Tigecycline administration showed a tendency of better clinical effectiveness in lowering inhospital mortality (17% vs 35%; p=0.083; OR=0.49; NNT=5 and worse clinical outcome / GOS ≤ 2 (20% vs 38% ; p=0.096; OR=0.41; NNT=6. LOS ≥ 15 hari ( 40% vs 27%; p=0.243; OR=1.81; NNT=8.Conclusion: Tigecycline showed anti-inflammatory and neuroprotective activities. These activities were associated with improved clinical outcome in patients with SSICH after hematoma evacuation.

  18. Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Brock, C; Brock, B; Aziz, Q

    2017-01-01

    The vagus nerve is a central component of cholinergic anti-inflammatory pathways. We sought to evaluate the effect of bilateral transcutaneous cervical vagal nerve stimulation (t-VNS) on validated parameters of autonomic tone and cytokines in 20 healthy subjects. 24 hours after t...

  19. MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis

    Czech Academy of Sciences Publication Activity Database

    Štika, Jiří; Vondráček, Jan; Hofmanová, Jiřina; Šimek, V.; Kozubík, Alois

    2006-01-01

    Roč. 237, č. 2 (2006), s. 263-271 ISSN 0304-3835 R&D Projects: GA ČR(CZ) GA524/03/0766 Institutional research plan: CEZ:AV0Z50040507 Keywords : cell differentiation * leukaemia * HL-60 cells Subject RIV: BO - Biophysics Impact factor: 3.277, year: 2006

  20. Anti-tumour necrosis factor-alpha activity in Ixodes ricinus saliva

    Czech Academy of Sciences Publication Activity Database

    Koník, Peter; Slavíková, Veronika; Salát, Jiří; Řezníčková, Jana; Dvorožňáková, E.; Kopecký, Jan

    2006-01-01

    Roč. 28, č. 12 (2006), s. 649-656 ISSN 0141-9838 R&D Projects: GA ČR GA524/05/0811; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Ixodes ricinus * tick saliva * TNF Subject RIV: EC - Immunology Impact factor: 2.009, year: 2006

  1. Analysis of relationship between tumor necrosis factor alpha gene (g308a polymorphism with preterm labor

    Directory of Open Access Journals (Sweden)

    Lobat Jafarzadeh

    2013-01-01

    Conclusions: There is no significant association between PTD and either maternal or fetal TNF-α −308 polymorphism and frequency ofGAmutation is not significantly increased in mothers and neonates delivered preterm. It means that the presence of this mutation by itself does not modify the overall risk of PTD. Investigations on the combination of various polymorphisms indifferent genes are recommended to achieve more accurate results.

  2. A role for tumor necrosis factor-alpha in ischemia and ischemic preconditioning

    LENUS (Irish Health Repository)

    Watters, Orla

    2011-08-02

    Abstract During cerebral ischemia, elevation of TNF-α and glutamate to pathophysiological levels may induce dysregulation of normal synaptic processes, leading ultimately to cell death. Previous studies have shown that patients subjected to a mild transient ischemic attack within a critical time window prior to a more severe ischemic episode may show attenuation in the clinical severity of the stroke and result in a more positive functional outcome. Studies with organotypic hippocampal cultures and mixed primary hippocampal cultures have shown that prior incubation with low concentrations of glutamate and TNF-α increase the resistance of neurones to a subsequent insult from glutamate, AMPA and NMDA, while co-exposure of TNF-α and for example AMPA may have neuroprotective effects compared to cultures exposed to excitotoxic agents alone. In addition our work has shown that although glutamate and TNF-α pretreatment induces analogous levels of desensitisation of the intracellular calcium dynamics of neurons under resting conditions and in response to acute glutamate stimulation, their downstream signalling pathways involved in this response do not converge. Glutamate and TNF-α would appear to have opposing effects on resting Ca2+ levels which supports the proposal that they have distinct modes of preconditioning.

  3. Tumor necrosis factor alpha (TNF alpha) in human skin : A comparison of different antibodies for immunohistochemistry

    NARCIS (Netherlands)

    van der Laan, N; de Leij, LFMH; Buurman, W; Timens, W; ten Duis, HJ

    Conflicting results have been reported regarding the localization and presence of TNF alpha in normal human skin, To study TNF alpha expression, we tested a panel of antibodies directed against human TNF alpha, First, antibodies were tested for immunoreactivity on cytospots of isolated

  4. Reduction of Burn Progression with Topical Delivery of (Antitumor Necrosis Factor-alpha )-Hyaluronic Acid Conjugates

    Science.gov (United States)

    2012-01-01

    delivery of semapimod in a pig model,28 while systemic delivery of curcumin has shown a positive effect in reducing burn wound progression by 50% in a rat...1366–72. 48. Singer AJ, Taira BR, Lin F, Lim T, Anderson R, McClain SA, Clark RA. Curcumin reduces injury progression in a rat comb burn model. J

  5. The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

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    Omoigui Sota

    2007-03-01

    Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.

  6. Expression of interleukin-6 by a recombinant rabies virus enhances its immunogenicity as a potential vaccine.

    Science.gov (United States)

    Luo, Jun; Zhang, Boyue; Wu, Yuting; Tian, Qin; Zhao, Jing; Lyu, Ziyu; Zhang, Qiong; Mei, Mingzhu; Luo, Yongwen; Guo, Xiaofeng

    2017-02-07

    Several studies have confirmed that interleukin-6 (IL6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. In the present study, recombinant rabies virus (RABV) expressing canine IL6 (rHEP-CaIL6) was rescued and its pathogenicity and immunogenicity were investigated in mice. We demonstrated that mice received a single intramuscular immunization with rHEP-CaIL6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (VNA) as well as anti-RABV antibodies compared with mice immunized with the parent strain. Moreover, survival rates of mice immunized with rHEP-CaIL6 were higher compared with mice immunized with parent HEP-Flury according to the challenge assay. Flow cytometry further confirmed that immunization with rHEP-CaIL6 induced the strong recruitment of mature B cells and CD8 + T cells to lymph nodes, which may partially explain the high levels of VNA and enhanced cellular immunity. Quantitative real-time PCR indicated that rHEP-CaIL6 induced stronger inflammatory and immune responses in the central nervous system, which might have allowed virus clearance in the early infection phase. Furthermore, mice infected intranasally with rHEP-CaIL6 developed no clinical symptoms while mice infected with HEP-Flury showed piloerection. In summary, these data indicate that rHEP-CaIL6 induces a strong, protective immune response with a good safety profile. Therefore, a recombinant RABV strain expressing canine IL6 may aid the development of an effective, safe attenuated rabies vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells

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    Yang, R.; Lin, Q.; Gao, H.B.; Zhang, P. [Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai (China)

    2014-02-17

    In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.

  8. Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma.

    Science.gov (United States)

    Matsuo, Koji; Hasegawa, Kosei; Yoshino, Kiyoshi; Murakami, Ryusuke; Hisamatsu, Takeshi; Stone, Rebecca L; Previs, Rebecca A; Hansen, Jean M; Ikeda, Yuji; Miyara, Akiko; Hiramatsu, Kosuke; Enomoto, Takayuki; Fujiwara, Keiichi; Matsumura, Noriomi; Konishi, Ikuo; Roman, Lynda D; Gabra, Hani; Fotopoulou, Christina; Sood, Anil K

    2015-09-01

    We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels. A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined. Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P<0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P=0.006). Advanced OCCC (hazard ratio [HR] 3.38, P<0.0001), thrombocytosis (HR 1.42, P=0.032) and elevated IL-6 (HR 8.90, P=0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P<0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P<0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P=0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P=0.07). Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Interleukin-6 Gene Promoter Polymorphisms and Cardiovascular Risk Factors. A family study

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    Iris Paola Guzmán-Guzmán

    2010-01-01

    Full Text Available Interleukin-6 (IL-6 is a cytokine involved in inflammatory process, as well as in glucose and lipid metabolism. Several studies of the biological relevance of IL-6 gene polymorphisms have indicated a relationship with cardiovascular disease. The aim of this study was to assess whether the –174 G/C and –572 G/C of IL-6 gene polymorphisms are associated with cardiovascular risk factors in Mexican families. Ninety members of 30 Mexican families, in which an index case (proband had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical and hematological parameters. High sensitivity C- reactive protein levels were measurement for nephelometric analysis. Screening for both polymorphisms studied was performed by PCR-RFLP. In the parents, both polymorphisms were in Hardy-Weinberg's equilibrium. The genotypes –174 GC/CC were associated with T2D (OR = 1.23, IC95% 1.01–1.5 and highest levels of hsCRP (p = 0.02, whereas genotype –572 GG was associated with T2D (OR = 1.24, IC95% 1.04–1.47 with an inflammatory state determined by the increase in the leukocyte count (OR = 1.24, IC95% 1.02–1.51. The genotypes –174 GC/CC and –572 GG may confer susceptibility for the development of subclinical inflammation and type 2 diabetes in Mexican families.

  10. Serum Interleukin-6, insulin, and HOMA-IR in male individuals with colorectal adenoma.

    Science.gov (United States)

    Sasaki, Yu; Takeda, Hiroaki; Sato, Takeshi; Orii, Tomohiko; Nishise, Shoichi; Nagino, Ko; Iwano, Daisuke; Yaoita, Takao; Yoshizawa, Kazuya; Saito, Hideki; Tanaka, Yasuhisa; Kawata, Sumio

    2012-01-15

    It is widely acknowledged that chronic low-grade inflammation plays a key role in the development of obesity-related insulin resistance and type 2 diabetes. The level of circulating interleukin-6 (IL-6), one of the major proinflammatory adipokines, is correlated with obesity and insulin resistance, which are known to be risk factors for colorectal adenoma. We examined the association between the circulating level of IL-6 and the presence of colorectal adenoma. In a total colonoscopy-based cross-sectional study conducted between January and December 2008, serum levels of IL-6 were measured in samples of venous blood obtained from 336 male participants attending health checkups (118 individuals with colorectal adenoma and 218 age-matched controls) after an overnight fast. In the colorectal adenoma group, the median levels of serum IL-6 (1.24 vs. 1.04 pg/mL; P = 0.01), triglyceride, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were to be significantly higher than those in the control group. When restricted to individuals with adenoma, levels of IL-6 were positively correlated with body mass index, insulin, and HOMA-IR. Multiple logistic analyses adjusted to include insulin or HOMA-IR showed that high levels of IL-6 were associated with the presence of colorectal adenoma. There was no significant interaction of IL-6 with HOMA-IR to modify this association. Our findings suggest that increased serum levels of IL-6 are positively associated with the presence of colorectal adenoma in men, independently of insulin and HOMA-IR. ©2011 AACR.

  11. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis

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    Masahiko Mihara

    2011-02-01

    .Keywords: interleukin-6, tocilizumab, efficacy, safety, mode of action

  12. Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis.

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    Hiroto Kinoshita

    Full Text Available Interleukin-6 (IL-6 is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial-stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6-positive cells in the stroma showed positive staining for the fibroblast marker α-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6(-/- mice with wild-type (WT mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6(-/- mice, compared with WT mice. Impaired tumor development in IL-6(-/- mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3-related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell-conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1 receptor antagonist and siRNA inhibition of IL-1α in the fibroblasts. IL-1α mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1α in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis.

  13. Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice.

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    Karol Kaminski

    2011-04-01

    Full Text Available Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO. The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice.

  14. Interleukin-6 is not essential for bone turnover in hypothyroid mice.

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    Maria Gorska

    2008-01-01

    Full Text Available Interleukin-6 (IL-6 has been shown to be involved in the pathogenesis of several bone diseases characterized by an imbalance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b and osteocalcin in IL-6-deficient mice to assess the role of IL-6 in bone metabolism in hypothyroidism in mice. C57BL/6J (wild-type; WT and C57BL/6J(IL6-/-Kopf (IL-6 knock-out; IL6KO mice randomly divided into 4 groups with 10 in each one: 1/ WT mice in hypothyroidism (WT-ht, 2/ WT controls, 3/ IL6KO mice with hypothyroidism (IL6KO-ht and 4/ IL6KO controls. Experimental model of hypothyroidism was induced by intraperitoneal injection of propylthiouracyl. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentrations of TRACP 5b (median and interquartile ranges were significantly decreased in both groups of mice with hypothyroidism: WT (3.2 (2.5-4.7 U/l and IL6KO (2.6 (1.8-3.5 U/l as compared to the respective controls. Similarly, serum osteocalcin levels were significantly reduced in both groups of mice in experimental hypothyroidism: WT (25.8 (23.0-28.2 ng/ml and IL6KO (21.5(19.0-24.6 ng/ml in comparison to the respective controls. There were no significant differences in bone turnover markers between IL6KO and WT mice both in hypothyroid and control animals. The results of the present study suggest that IL-6 does not play an important role in bone turnover in both euthyroid and hypothyroid mice.

  15. Meta-analysis of interleukin-6 concentration in peritoneal fluid of women with endometriosis

    International Nuclear Information System (INIS)

    Zuo Liandong; Zheng Hui; Li Hongyi

    2003-01-01

    To investigate whether the Interleukin-6 (IL-6) concentration in peritoneal fluid of patients with endometriosis (EM) is higher than that of healthy, synthetic quantitative analysis was used to study international literatures on IL-6 in peritoneal fluid of women with EM by means of Meta-analysis. The results showed that IL-6 levels of ELISA in the women with EM were -0.472-3.974 times of standard deviation higher than those in the healthy control group. Regardless of measurement methods, -0.73-3.45 times of standard deviation was higher. Both results could not generally think that the IL-6 in peritoneal fluid of EM patient was higher than that of normal persons. However, when EM was diagnosed at the time of laparoscopy or surgery and staged according to AFS, I-II stage were attributed to EM1, III-IV stage were EM2. It was found by Meta-analysis that the elevated IL-6 levels had a mutual relation with the severity of EM: The levels of EM1 were -4.807-5.608 times of standard deviation higher than those of then healthy, with no significant difference (P>0.05), whereas those of EM2 were 0.54-5.34 times or 1.13-5.46 times of standard deviation higher than those of EM1 or healthy, respectively, both with significant difference. The higher the IL-6 levels of the patients had in peritoneal fluid, the more serious EM were. The dysregulation of IL-6 responses might play a role in the pathophysiology of EM

  16. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression

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    Patchen, M.L.; MacVittie, T.J.; Williams, J.L.; Schwartz, G.N.; Souza, L.M. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1991-02-01

    Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.

  17. Cellular and Oxidative Mechanisms Associated with Interleukin-6 Signaling in the Vasculature

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    Sean P. Didion

    2017-11-01

    Full Text Available Reactive oxygen species, particularly superoxide, promote endothelial dysfunction and alterations in vascular structure. It is increasingly recognized that inflammatory cytokines, such as interleukin-6 (IL-6, contribute to endothelial dysfunction and vascular hypertrophy and fibrosis. IL-6 is increased in a number of cardiovascular diseases, including hypertension. IL-6 is also associated with a higher incidence of future cardiovascular events and all-cause mortality. Both immune and vascular cells produce IL-6 in response to a number of stimuli, such as angiotensin II. The vasculature is responsive to IL-6 produced from vascular and non-vascular sources via classical IL-6 signaling involving a membrane-bound IL-6 receptor (IL-6R and membrane-bound gp130 via Jak/STAT as well as SHP2-dependent signaling pathways. IL-6 signaling is unique because it can also occur via a soluble IL-6 receptor (sIL-6R which allows for IL-6 signaling in tissues that do not normally express IL-6R through a process referred to as IL-6 trans-signaling. IL-6 signaling mediates a vast array of effects in the vascular wall, including endothelial activation, vascular permeability, immune cell recruitment, endothelial dysfunction, as well as vascular hypertrophy and fibrosis. Many of the effects of IL-6 on vascular function and structure are representative of loss or reductions in nitric oxide (NO bioavailability. IL-6 has direct effects on endothelial nitric oxide synthase activity and expression as well as increasing vascular superoxide, which rapidly inactivates NO thereby limiting NO bioavailability. The goal of this review is to highlight both the cellular and oxidative mechanisms associated with IL-6-signaling in the vascular wall in general, in hypertension, and in response to angiotensin II.

  18. Discovery and Characterization of a Potent Interleukin-6 Binding Peptide with Neutralizing Activity In Vivo.

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    Sheila Ranganath

    Full Text Available Interleukin-6 (IL-6 is an important member of the cytokine superfamily, exerting pleiotropic actions on many physiological processes. Over-production of IL-6 is a hallmark of immune-mediated inflammatory diseases such as Castleman's Disease (CD and rheumatoid arthritis (RA. Antagonism of the interleukin IL-6/IL-6 receptor (IL-6R/gp130 signaling complex continues to show promise as a therapeutic target. Monoclonal antibodies (mAbs directed against components of this complex have been approved as therapeutics for both CD and RA. To potentially provide an additional modality to antagonize IL-6 induced pathophysiology, a peptide-based antagonist approach was undertaken. Using a combination of molecular design, phage-display, and medicinal chemistry, disulfide-rich peptides (DRPs directed against IL-6 were developed with low nanomolar potency in inhibiting IL-6-induced pSTAT3 in U937 monocytic cells. Targeted PEGylation of IL-6 binding peptides resulted in molecules that retained their potency against IL-6 and had a prolongation of their pharmacokinetic (PK profiles in rodents and monkeys. One such peptide, PN-2921, contained a 40 kDa polyethylene glycol (PEG moiety and inhibited IL-6-induced pSTAT3 in U937 cells with sub-nM potency and possessed 23, 36, and 59 h PK half-life values in mice, rats, and cynomolgus monkeys, respectively. Parenteral administration of PN-2921 to mice and cynomolgus monkeys potently inhibited IL-6-induced biomarker responses, with significant reductions in the acute inflammatory phase proteins, serum amyloid A (SAA and C-reactive protein (CRP. This potent, PEGylated IL-6 binding peptide offers a new approach to antagonize IL-6-induced signaling and associated pathophysiology.

  19. Anorexia, fatigue, and plasma interleukin-6 levels in chronic hemodialysis patients.

    Science.gov (United States)

    Bossola, Maurizio; Luciani, Giovanna; Giungi, Stefania; Tazza, Luigi

    2010-01-01

    This study aimed at evaluating the possible relationship between anorexia and fatigue in hemodialysis (HD) patients and at measuring the plasma levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in HD patients with or without anorexia and/or fatigue. The first question of the Hemodialysis Study Appetite questionnaire was used to assess the appetite of the HD patients and the vitality scale of the SF-36 to assess fatigue. The Charlson Comorbidity Index was assessed in each patient. Seventy-six HD patients were studied. Forty-four were males and 32 females. Thirty-two were classified as not-anorexic and not-fatigued, 12 as not-anorexic but fatigued, 6 as anorexic and not-fatigued, and 26 as anorexic and fatigued. Plasma IL-6 levels (pg/mL) were significantly higher in anorexic and fatigued patients (10.9 ± 11.9) than in not-anorexic and not-fatigued (1.6 ± 0.6) (p anorexic but not-fatigued patients (1.8 ± 1.7) (p anorexic but fatigued patients (3.1 ± 1.5), the difference was not statistically significant (p = 0.058). The plasma CRP levels (mg/dL) also were significantly higher in anorexic and fatigued patients (9.2 ± 6.3) than in not-anorexic and not-fatigued patients (4.1 ± 4.5), in anorexic but not-fatigued patients (2.5 ± 1.6), and in not-anorexic but fatigued patients (4.1 ± 4.4) (p = 0.001). The presence of both anorexia and fatigue in chronic HD patients is associated with significantly higher levels of plasma IL-6 and CRP and a higher frequency of comorbidities.

  20. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

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    Izziki Mohamed

    2009-01-01

    Full Text Available Abstract Background Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH. Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6. Methods To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6-/- and wild-type (IL-6+/+ mice exposed to hypoxia for 2 weeks. Results Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines. Conclusion These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.

  1. Interleukin-6 and interleukin-10 plasma levels and mRNA expression in polytrauma patients.

    Science.gov (United States)

    Sapan, Heber B; Paturusi, Idrus; Islam, Andi Asadul; Yusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muhammmad Nasrum; Pusponegoro, Aryono D; Arief, Syafrie K; Labeda, Ibrahim; Rendy, Leo; Hatta, Mochammad

    2017-12-01

    Host response to polytrauma occasionally has unpredictable outcomes. Immune response is a major factor influencing patient's outcome. This study evaluated the interaction of two main cytokines in immune response after major trauma, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10). Plasma level of these cytokines is determined by mRNA expression of these cytokines genes which may decide the outcome of polytrauma patients. This prospective multicenter trial held at four trauma centers enrolled 54 polytrauma patients [Injury Severity Score (ISS) ≥ 16]. Plasma levels and mRNA expression of IL-6 and IL-10 were measured for 5 days after trauma. Clinical evaluation was conducted to observe whether patients endured multiple organ dysfunction syndrome (MODS) and death. MODS evaluation was performed using sequential organ failure assessment (SOFA). Trauma load which in this study is represented with ISS, plasma level, expression of cytokine genes and patient's outcome were examined with correlation test and statistical analysis. The elevated IL-6/IL-10 ratio indicated increased activity of systemic inflammation response, especially pro-inflammation response which bears higher probability of progressing to MODS and death. The decline of IL-6/IL-10 ratio with heavy trauma load (ISS > 30) showed that compensatory anti-inflammation response syndrome (CARS) state was more dominant than systemic inflammatory response syndrome (SIRS), indicating that malfunction and failure of immune system eventually lead to MODS and deaths. The statistical significance in plasma level of cytokines was found in the outcome group which was defined as bearing a low trauma load but mortality. The pattern of cytokine levels in inflammation response has great impact on the outcome of polytrauma patients. Further study at the genetic level is needed to investigate inflammation process which may influence patient's outcome. Copyright © 2017 Daping Hospital and the Research Institute of

  2. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Association of maternal and neonatal plasma interleukin-6 levels in relation to model of delivery

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    Mahmoud Imani

    2011-07-01

    Full Text Available Background: Cytokines play an important role during labor of full – or pretern delivery. In umbilical cord blood, Interleukin-6 (IL-6 was thought to be a marker of defense to stress, surgery and infection. The aim of this study was to investigate the cytokine IL-6 concentrations in the mother and neonate depends on the mode of the delivery.Materials and Method: This study was done on mothers and neonates in 80 single term deliveries (vaginal and cesarean in Mahdieh Hospital in Tehran. Age of mothers was 21-39 years old, parity was 1 and 2. There wasn't history of underlying disease and drug usage in mothers and neonate was AGA and apgar was more than 8. There wasn't clinical evidence of infection in neonate and mothers. IL-6 was evaluated by enzyme-immunoassays in maternal serum and neonatal umbilical cord. Data were analyzed with SPSS and were applied fishers exact test for compare means.Results: There were 37 vaginal deliveries and 43cesarean section. The mean (±standard error of maternal IL-6 concentration in vaginal delivery (0.18±0.02 was significantly (P=0.000 higher than cesarean section (0.1±0.02 and neonatal IL-6 concentration in vaginal delivery (0.17±0.03 was significantly (P=0.000 higher than cesarean section (0.07±0.01.Conclusion: Results show that vaginal delivery cause to increase IL-6 compared to cesarean section in mother and neonate

  4. Role of interleukin-6 levels in cardiovascular autonomic dysfunction in type 2 diabetic patients

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    Shinohara, Tetsuji; Takahashi, Naohiko; Kakuma, Tetsuya; Hara, Masahide; Yoshimatsu, Hironobu [Oita University, Department of Internal Medicine 1, Faculty of Medicine, Yuhu, Oita (Japan); Yufu, Kunio; Anan, Futoshi; Nakagawa, Mikiko; Saikawa, Tetsunori [Oita University, Department of Cardiovascular Science, Oita (Japan)

    2008-09-15

    Increased serum interleukin-6 (IL-6) levels are associated with an increased risk of cardiovascular disease, and cardiovascular autonomic dysfunction is associated with high mortality in type 2 diabetic patients. However, the relationship between IL-6 levels and cardiovascular autonomic dysfunction has not been fully elucidated. The aim of this study was to determine whether serum IL-6 levels are associated with cardiovascular autonomic dysfunction in type 2 diabetic patients. Eighty type 2 diabetic patients who did not have organic heart disease were categorized into a high IL-6 group (>2.5 pg/ml, n= 0, age 59{+-}12 years) or a non-high IL-6 group (<2.5 pg/ml, n=40, 61{+-}12 years). Cardiac autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations and {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. The body mass index values (BMI), fasting insulin levels and homeostasis model assessment index values were higher in the high IL-6 group than in the non-high IL-6 group (p<0.01). Early and delayed {sup 123}I-MIBG myocardial uptake values were lower (p<0.01), and the percent washout rate of {sup 123}I-MIBG was higher (p<0.05) in the high IL-6 group than in the non-high IL-6 group. Furthermore, multiple regression analysis revealed that the IL-6 level was independently predicted by the BMI and the myocardial uptake of {sup 123}I-MIBG during the delayed phase. The results indicate that elevated IL-6 levels are associated with depressed cardiovascular autonomic function and obesity in type 2 diabetic patients. (orig.)

  5. Interleukin-6 maintains glucose homeostasis to support strenuous masseter muscle activity in mice.

    Science.gov (United States)

    Tsuchiya, Masahiro; Kiyama, Tomomi; Tsuchiya, Shinobu; Takano, Hirohisa; Nemoto, Eiji; Sasaki, Keiichi; Watanabe, Makoto; Sugawara, Shunji; Endo, Yasuo

    2012-06-01

    The cytokine interleukin-6 (IL-6) is released from working skeletal muscles and reportedly plays key roles in their glucose homeostasis. However, it is unclear whether IL-6 plays such roles in the masseter muscle (MM), which is important in normal and pathological chewing behaviors, such as bruxism and/or prolonged clenching. When restrained (R+) in a narrow cylinder blocked at the front end with a thin plastic strip, a mouse gnaws away (G+) the strip to escape. The absolute weight of plastic gnawed away serves as an index of MM activity. Using this model, we examined the roles of IL-6 in MM with the following results. R+G+ increased the expression levels of IL-6 and glucose transporter 4 (Glut4) mRNAs in MM and the serum level of IL-6 protein. IL-6-deficient mice exhibited about 60% less gnawing activity than wild-type mice at 3-4 h after the start of R+G+, slower recovery of glycogen levels (indicating poorer glucose supply) in MM after R+G+, and no significant change in Glut4 mRNA in MM upon R+G+. During an R+G+ test conducted after "training" (repeated R+G+ sessions), wild-type mice exhibited greater gnawing activity than untrained controls, but no increase in IL-6 mRNA in MM. IL-6 mRNA increased in MM when hard food was eaten by mice raised on soft food for 3 weeks from weaning, but not in those raised on (accustomed to) hard food. Thus, IL-6 may maintain glucose homeostasis in MM in support of unusually strenuous activity, but not of accustomed activity levels.

  6. Discovery and Characterization of a Potent Interleukin-6 Binding Peptide with Neutralizing Activity In Vivo

    Science.gov (United States)

    Ranganath, Sheila; Bhandari, Ashok; Avitahl-Curtis, Nicole; McMahon, Jaimee; Wachtel, Derek; Zhang, Jenny; Leitheiser, Christopher; Bernier, Sylvie G.; Liu, Guang; Tran, Tran T.; Celino, Herodion; Tobin, Jenny; Jung, Joon; Zhao, Hong; Glen, Katie E.; Graul, Chris; Griffin, Aliesha; Schairer, Wayne C.; Higgins, Carolyn; Reza, Tammi L.; Mowe, Eva; Rivers, Sam; Scott, Sonya; Monreal, Alex; Shea, Courtney; Bourne, Greg; Coons, Casey; Smith, Adaline; Tang, Kim; Mandyam, Ramya A.; Masferrer, Jaime; Liu, David; Patel, Dinesh V.; Fretzen, Angelika; Murphy, Craig A.; Milne, G. Todd; Smythe, Mark L.; Carlson, Kenneth E.

    2015-01-01

    Interleukin-6 (IL-6) is an important member of the cytokine superfamily, exerting pleiotropic actions on many physiological processes. Over-production of IL-6 is a hallmark of immune-mediated inflammatory diseases such as Castleman’s Disease (CD) and rheumatoid arthritis (RA). Antagonism of the interleukin IL-6/IL-6 receptor (IL-6R)/gp130 signaling complex continues to show promise as a therapeutic target. Monoclonal antibodies (mAbs) directed against components of this complex have been approved as therapeutics for both CD and RA. To potentially provide an additional modality to antagonize IL-6 induced pathophysiology, a peptide-based antagonist approach was undertaken. Using a combination of molecular design, phage-display, and medicinal chemistry, disulfide-rich peptides (DRPs) directed against IL-6 were developed with low nanomolar potency in inhibiting IL-6-induced pSTAT3 in U937 monocytic cells. Targeted PEGylation of IL-6 binding peptides resulted in molecules that retained their potency against IL-6 and had a prolongation of their pharmacokinetic (PK) profiles in rodents and monkeys. One such peptide, PN-2921, contained a 40 kDa polyethylene glycol (PEG) moiety and inhibited IL-6-induced pSTAT3 in U937 cells with sub-nM potency and possessed 23, 36, and 59 h PK half-life values in mice, rats, and cynomolgus monkeys, respectively. Parenteral administration of PN-2921 to mice and cynomolgus monkeys potently inhibited IL-6-induced biomarker responses, with significant reductions in the acute inflammatory phase proteins, serum amyloid A (SAA) and C-reactive protein (CRP). This potent, PEGylated IL-6 binding peptide offers a new approach to antagonize IL-6-induced signaling and associated pathophysiology. PMID:26555695

  7. Cardiovascular Response and Serum Interleukin-6 Level in Concentric Vs. Eccentric Exercise.

    Science.gov (United States)

    Agarwal, Mayank; Singh, Shraddha; Narayan, Jagdish; Pandey, Shivani; Tiwari, Sunita; Sharma, Priyanka

    2017-04-01

    Cardiovascular Disease (CVD) is a leading cause of morbidity and mortality in India. Resistance exercise is strongly recommended for implementation in CVD prevention programs. Dynamic resistance exercise comprises of concentric (muscle shortening) and eccentric (muscle lengthening) phase. The contraction of skeletal muscle promotes the synthesis and secretion of cytokines and peptides from myocytes, known as 'myokines'. Interleukin-6 (IL-6) is the first myokine to be released in the blood in response to exercise. To compare the cardiovascular response and serum IL-6 level in concentric and eccentric exercise done at same absolute workload. In this non-randomised crossover study 24, apparently healthy and young male adults performed an acute bout of concentric and eccentric exercise. Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Heart Rate (HR), Mean Arterial Pressure (MAP), Pulse Pressure (PP) and serum IL-6 were measured just before and immediately after exercise. Paired t-test or Wilcoxon signed-rank test were applied to compare the data within-group and in-between group. SBP, HR, MAP, PP, DBP and IL-6 level increased significantly after both, concentric and eccentric exercise. The mean change in SBP, HR, MAP, PP, and IL-6 after concentric exercise (18.54±3.06, 57.21±10.73, 8.35±1.40, 15.25±5.29, 5.40±3.13 respectively) was significantly higher than after eccentric exercise (13.38±1.72, 43.25±8.34, 6.50±1.0, 10.21±3.16, 4.36±2.54 respectively). A non-significant rise in DBP was obtained after concentric exercise (3.25±2.79) as compared to eccentric exercise (3.08±1.89). Eccentric exercise not only caused a lesser cardiovascular demand as compared to concentric exercise but also a significant increment in IL-6 level. Exercise-induced IL-6 may prevent the initiation and development of CVD. Hence, eccentric exercise training might be recommended for reducing morbidity and mortality in individuals with- or at a risk of developing CVD.

  8. Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy.

    Science.gov (United States)

    Ptaszynska-Kopczynska, Katarzyna; Szpakowicz, Anna; Marcinkiewicz-Siemion, Marta; Lisowska, Anna; Waszkiewicz, Ewa; Witkowski, Marcin; Jakim, Piotr; Galar, Bogdan; Musial, Wlodzimierz J; Kamiński, Karol A

    2017-08-01

    Increased expression of interleukin-6 (IL-6) has been described in left ventricular dysfunction in the course of chronic heart failure. Cardiac resynchronization therapy (CRT) is a unique treatment method that may reverse the course of chronic heart failure (CHF) with reduced ejection fraction (HF-REF). We aimed to evaluate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients, with particular emphasis on CRT effects. The study enrolled 88 stable HF-REF patients (63.6 ±11.1 years, 12 females, EF < 35%) and 35 comorbidity-matched controls (63.5 ±9.8 years, 7 females). Forty-five HF-REF patients underwent CRT device implantation and were followed up after 6 months. Serum concentrations of IL-6, sIL-6R and sgp130 were determined using ELISA kits. The HF-REF patients had higher IL-6 (median: 2.6, IQR: 1.6-3.8 vs. 2.1, IQR: 1.4-3.1 pg/ml, p = 0.03) and lower sIL-6R concentrations compared to controls (median: 51, IQR: 36-64 vs. 53. IQR 44-76 ng/ml, p = 0.008). There was no significant difference between sgp130 concentrations. In the HF-REF group IL-6 correlated negatively with EF ( r = -0.5, p = 0.001) and positively with BNP ( r = 0.5, p = 0.008) and CRP concentrations ( r = 0.4, p = 0.02). Patients who presented a positive response after CRT showed a smaller change of sIL-6R concentration compared to nonresponders (ΔsIL-6R: -0.2 ±7.1 vs. 7 ±14 ng/ml; p = 0.04). HF-REF patients present higher IL-6 and lower sIL-6R levels. IL-6 concentration reflects their clinical status. CRT-related improvement of patients' functional status is associated with a smaller change of sIL-6R concentration in time.

  9. Interleukin-6 and airflow limitation in chemical warfare patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Davood Attaran

    2010-09-01

    disease, interleukin-6, inflammation, chemical warfare

  10. Interleukin-6 Attenuates Serotonin 2A Receptor Signaling by Activating the JAK-STAT Pathway

    Science.gov (United States)

    Donegan, Jennifer J.; Patton, Michael S.; Chavera, Teresa S.; Berg, Kelly A.; Morilak, David A.

    2015-01-01

    The serotonin 2A (5-HT2A) receptor and the proinflammatory cytokine, interleukin-6 (IL-6), have both been implicated in psychiatric disorders. Previously, we demonstrated that these molecules both facilitate cognitive flexibility, a prefrontal cortex-mediated executive function impaired in multiple mental illnesses. In this study, we tested the hypothesis that IL-6 influences 5-HT2A receptor signaling, providing a potential mechanism by which this cytokine may influence behavior. We first demonstrated that 5-HT2A receptors and IL-6–mediated STAT3 phosphorylation colocalize in cells of the prefrontal cortex, providing the neuroanatomical substrate for a potential interaction. In the neuronally derived A1A1 cell line, which expresses both IL-6 and 5-HT2A receptors, we found that IL-6 attenuates inositol phosphate (IP) accumulation in response to the 5-HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), suggesting that IL-6 can regulate 5-HT2A receptor function. To identify the signaling pathway(s) that mediate this effect, we measured DOI-mediated IP accumulation in the presence of IL-6 and either the JAK-STAT inhibitor 124 [(9β,10α,16α,23E)-2,16,20,25-tetrahydroxy-9-methyl-19-norlanosta-1,5,23-triene-3,11,22-trione], JSI-124, or the extracellular signal-regulated kinase inhibitor, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD-98059). The IL-6 effect was blocked by JSI-124 but not PD-98059. Furthermore, silencing RNA knockdown of either JAK or STAT blocked the IL-6 effect, suggesting that IL-6–induced JAK-STAT activation can regulate 5-HT2A receptor signaling. Finally, to determine if IL-6 specifically regulates the 5-HT2A receptor system, we measured IP production mediated by another Gq-coupled receptor, bradykinin B2. IL-6 had no effect on bradykinin-mediated IP accumulation, suggesting that regulation may occur at the 5-HT2A receptor. These results may provide clues to the pathologic mechanisms underlying certain psychiatric disorders and may

  11. Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

    International Nuclear Information System (INIS)

    Brozek, Wolfgang; Bises, Giovanna; Fabjani, Gerhild; Cross, Heide S; Peterlik, Meinrad

    2008-01-01

    Many cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.e. IL-1β, prostaglandin E 2 , 17β-estradiol, and 1,25-dihydroxyvitamin D 3 , on expression and synthesis of the cytokine at different stages of tumour progression. We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the IL-6 gene promoter. IL-6 mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml) to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10 -7 M) reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the IL-6 promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the IL-6 gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-myc proto-oncogene expression. These effects were inhibited by 10 -8 M 1,25-dihydroxyvitamin D 3 . In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally affected, if at all, by PGE 2 , 1,25-dihydroxyvitamin D

  12. Interleukin 6 Deficiency Modulates the Hypothalamic Expression of Energy Balance Regulating Peptides during Pregnancy in Mice

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Casanueva, Felipe F.; Diéguez, Carlos; García, María C.

    2013-01-01

    Pregnancy is associated with hyperphagia, increased adiposity and multiple neuroendocrine adaptations. Maternal adipose tissue secretes rising amounts of interleukin 6 (IL6), which acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. To explore the role of IL6 in the central mechanisms governing dam's energy homeostasis, early, mid and late pregnant (gestational days 7, 13 and 18) wild-type (WT) and Il6 knockout mice (Il6-KO) were compared with virgin controls at diestrus. Food intake, body weight and composition as well as indirect calorimetry measurements were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy) and agouti-related peptide (Agrp); and catabolic and anorectic neuropeptides: proopiomelanocortin (Pomc), corticotrophin and thyrotropin-releasing hormone (Crh and Trh) mRNA levels were determined by in situ hybridization. Real time-PCR and western-blot were used for additional tissue gene expression and protein studies. Non-pregnant Il6-KO mice were leaner than WT mice due to a decrease in fat but not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despite similar body weight gain than WT controls. A decreased fat utilization in absence of Il6 might explain this effect, as shown by increased respiratory exchange ratio (RER) in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in adipose tissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh expression was also stimulated at gestational day 13 and lack of Il6 blunted this effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor alpha (Il6ra), Pomc and Crh mRNA were observed. Il6 deficiency during this stage up-regulated Npy and Agrp expression, while restoring Pomc mRNA levels to virgin values. Together these results demonstrate that IL6/IL6Ra system modulates Npy/Agrp, Pomc and Trh expression during mouse pregnancy, supporting a role of IL6 in the central

  13. Interleukin 6 deficiency modulates the hypothalamic expression of energy balance regulating peptides during pregnancy in mice.

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Casanueva, Felipe F; Diéguez, Carlos; García, María C

    2013-01-01

    Pregnancy is associated with hyperphagia, increased adiposity and multiple neuroendocrine adaptations. Maternal adipose tissue secretes rising amounts of interleukin 6 (IL6), which acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. To explore the role of IL6 in the central mechanisms governing dam's energy homeostasis, early, mid and late pregnant (gestational days 7, 13 and 18) wild-type (WT) and Il6 knockout mice (Il6-KO) were compared with virgin controls at diestrus. Food intake, body weight and composition as well as indirect calorimetry measurements were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy) and agouti-related peptide (Agrp); and catabolic and anorectic neuropeptides: proopiomelanocortin (Pomc), corticotrophin and thyrotropin-releasing hormone (Crh and Trh) mRNA levels were determined by in situ hybridization. Real time-PCR and western-blot were used for additional tissue gene expression and protein studies. Non-pregnant Il6-KO mice were leaner than WT mice due to a decrease in fat but not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despite similar body weight gain than WT controls. A decreased fat utilization in absence of Il6 might explain this effect, as shown by increased respiratory exchange ratio (RER) in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in adipose tissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh expression was also stimulated at gestational day 13 and lack of Il6 blunted this effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor alpha (Il6ra), Pomc and Crh mRNA were observed. Il6 deficiency during this stage up-regulated Npy and Agrp expression, while restoring Pomc mRNA levels to virgin values. Together these results demonstrate that IL6/IL6Ra system modulates Npy/Agrp, Pomc and Trh expression during mouse pregnancy, supporting a role of IL6 in the central

  14. Low-Dose Pulsatile Interleukin-6 As a Treatment Option for Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Gautam Ghatnekar

    2017-05-01

    Full Text Available Diabetic peripheral neuropathy (DPN remains one of the most common and serious complications of diabetes. Currently, pharmacological agents are limited to treating the pain associated with DPN, and do not address the underlying pathological mechanisms driving nerve damage, thus leaving a significant unmet medical need. Interestingly, research conducted using exercise as a treatment for DPN has revealed interleukin-6 (IL-6 signaling to be associated with many positive benefits such as enhanced blood flow and lipid metabolism, decreased chronic inflammation, and peripheral nerve fiber regeneration. IL-6, once known solely as a pro-inflammatory cytokine, is now understood to signal as a multifunctional cytokine, capable of eliciting both pro- and anti-inflammatory responses in a context-dependent fashion. IL-6 released from muscle in response to exercise signals as a myokine and as such has a unique kinetic profile, whereby levels are transiently elevated up to 100-fold and return to baseline levels within 4 h. Importantly, this kinetic profile is in stark contrast to long-term IL-6 elevation that is associated with pro-inflammatory states. Given exercise induces IL-6 myokine signaling, and exercise has been shown to elicit numerous beneficial effects for the treatment of DPN, a causal link has been suggested. Here, we discuss both the clinical and preclinical literature related to the application of IL-6 as a treatment strategy for DPN. In addition, we discuss how IL-6 may directly modulate Schwann and nerve cells to explore a mechanistic understanding of how this treatment elicits a neuroprotective and/or regenerative response. Collectively, studies suggest that IL-6, when administered in a low-dose pulsatile strategy to mimic the body’s natural response to exercise, may prove to be an effective treatment for the protection and/or restoration of peripheral nerve function in DPN. This review highlights the studies supporting this assertion and

  15. Interleukin 6 and lipopolysaccharide binding protein - markers of inflammation in acute appendicitis.

    Science.gov (United States)

    Brănescu, C; Serban, D; Dascălu, A M; Oprescu, S M; Savlovschi, C

    2013-01-01

    The rate of incidence of acute appendicitis is 12% in the case of male patients and 25% in case of women, which represents about 7% of the world population. The appendectomy rate has remained constant (i.e. 10 out of 10,000 patients per year). Appendicitis most often occurs in patients aged between 11-40 years, on the threshold between the third and fourth decades, the average age being 31.3 years. Since the first appendectomy performed by Claudius Amyand (1681/6 -1740), on December, 6th, 1735 to our days, i.e., 270 years later, time has confirmed the efficiency of both the therapy method and the surgical solution. The surgical cure in case of acute appendicitis has proved to be acceptable within the most widely practised techniques in general surgery. The variety of clinical forms has reached all age ranges, which in its turn has resulted in a large number of semiotic signs. In the case of acute appendicitis, interdisciplinarity has allowed the transfer of concept and methodology transfer among many areas of expertise, aimed at a better, minute understanding of the inflammatory event itself. Acute appendicitis illustrates inflammation development at digestive level and provides for a diagnostic and paraclinical exploration which continually upgrades. The recent inclusion in the studies of the Lipopolysaccharide binding protein (LBP)- type inflammation markers has laid the foundation of the latter's documented presence in the case of acute appendicitis-related inflammation. Proof of the correlation between the histopathological, clinical and evolutive forms can be found by identifying and quantifying these inflammation markers. The importance of studying inflammation markers allows us to conduct studies going beyond the prognosis of the various stages in which these markers were identified. The present article shows the results of a 1-year monitoring of the inflammation markers' values for Interleukin-6 and Lipopolysaccharide binding protein (LBP)-types, both pre

  16. The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism.

    Science.gov (United States)

    von Loeffelholz, Christian; Lieske, Stefanie; Neuschäfer-Rube, Frank; Willmes, Diana M; Raschzok, Nathanael; Sauer, Igor M; König, Jörg; Fromm, Martin F; Horn, Paul; Chatzigeorgiou, Antonios; Pathe-Neuschäfer-Rube, Andrea; Jordan, Jens; Pfeiffer, Andreas F H; Mingrone, Geltrude; Bornstein, Stefan R; Stroehle, Peter; Harms, Christoph; Wunderlich, F Thomas; Helfand, Stephen L; Bernier, Michel; de Cabo, Rafael; Shulman, Gerald I; Chavakis, Triantafyllos; Püschel, Gerhard P; Birkenfeld, Andreas L

    2017-08-01

    Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical

  17. Interleukin-6 Deficiency Attenuates Retinal Ganglion Cell Axonopathy and Glaucoma-Related Vision Loss

    Directory of Open Access Journals (Sweden)

    Franklin D. Echevarria

    2017-05-01

    Full Text Available The pleotropic cytokine interleukin-6 (IL-6 is implicated in retinal ganglion cell (RGC survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT and IL-6 knock-out mice (B6;129S2-IL6tm1kopf/J; IL-6-/- after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model. IOP increased by 20% following microbead injection in both genotypes (p < 0.05. However, deficits in wound healing at the site of corneal injection were noted. In WT mice, elevated IOP produced degenerating axon profiles and decreased axon density in the optic nerve by 15% (p < 0.01. In IL-6-/- mice, axon density in the optic nerve did not differ between microbead- and saline-injected mice (p > 0.05 and degenerating axon profiles were minimal. Preservation of RGC axons was reflected in visual function, where visual acuity decreased significantly in a time-dependent manner with microbead-induced IOP elevation in WT (p < 0.001, but not IL-6-/- mice (p > 0.05. Despite this preservation of RGC axons and visual acuity, both microbead-injected WT and IL-6-/- mice exhibited a 50% decrease in anterograde CTB transport to the superior colliculus, as compared to saline-injected controls (p < 0.01. Assessment of glial reactivity revealed no genotype- or IOP-dependent changes in retinal astrocytes. IOP elevation decreased microglia density and percent retinal area covered in WT mice (p < 0.05, while IL-6-/- mice exhibited only a decrease in density (p < 0.05. Together, our findings indicate that two defining features of RGC axonopathy—axon transport deficits and structural degeneration of

  18. Interleukin-6 dynamics as a basis for an early-warning monitor for sepsis and inflammation in individual pigs.

    Science.gov (United States)

    Tambuyzer, Tim; De Waele, Tine; Chiers, Koen; Berckmans, Daniel; Goddeeris, Bruno M; Aerts, Jean-Marie

    2014-06-01

    Static interleukin-6 (IL-6) levels of pigs contain considerable individual differences, which obstruct the practical use of IL-6 for disease monitoring purposes. It was hypothesised that interleukin-6 (IL-6) dynamics could be used to quantify these individual differences and carries critical information of the individual pig infection status. Time series of IL-6 responses in 25 pigs were analysed before and after infection by Actinobacillus pleuropneumoniae. The results indicated that amplitude increases of IL-6 fluctuations of individual pigs rather than static IL-6 values should be used as indicator of the infection state. This study shows the added value for IL-6 time series analyses of individual pigs. These results are a first step towards the development of objective individualised methods for monitoring and early detection of sepsis and inflammation processes in pigs by integrating animal response dynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Drugs elevating extracellular adenosine administered in vivo induce serum colony-stimulating activity and interleukin-6 in mice

    Czech Academy of Sciences Publication Activity Database

    Weiterová, Lenka; Hofer, Michal; Pospíšil, Milan; Znojil, V.; Štreitová, Denisa

    2007-01-01

    Roč. 56, č. 4 (2007), s. 463-473 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP305/03/D050 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : extracellular adenosine * serum colony-stimulating activity * interleukin-6 Subject RIV: BO - Biophysics Impact factor: 1.505, year: 2007

  20. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

    Directory of Open Access Journals (Sweden)

    Wei Xia

    2015-01-01

    Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  1. Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age.

    Science.gov (United States)

    Graham, Alice M; Rasmussen, Jerod M; Rudolph, Marc D; Heim, Christine M; Gilmore, John H; Styner, Martin; Potkin, Steven G; Entringer, Sonja; Wadhwa, Pathik D; Fair, Damien A; Buss, Claudia

    2018-01-15

    Maternal inflammation during pregnancy increases the risk for offspring psychiatric disorders and other adverse long-term health outcomes. The influence of inflammation on the developing fetal brain is hypothesized as one potential mechanism but has not been examined in humans. Participants were adult women (N = 86) who were recruited during early pregnancy and whose offspring were born after 34 weeks' gestation. A biological indicator of maternal inflammation (interleukin-6) that has been shown to influence fetal brain development in animal models was quantified serially in early, mid-, and late pregnancy. Structural and functional brain magnetic resonance imaging scans were acquired in neonates shortly after birth. Infants' amygdalae were individually segmented for measures of volume and as seeds for resting state functional connectivity. At 24 months of age, children completed a snack delay task to assess impulse control. Higher average maternal interleukin-6 concentration during pregnancy was prospectively associated with larger right amygdala volume and stronger bilateral amygdala connectivity to brain regions involved in sensory processing and integration (fusiform, somatosensory cortex, and thalamus), salience detection (anterior insula), and learning and memory (caudate and parahippocampal gyrus). Larger newborn right amygdala volume and stronger left amygdala connectivity were in turn associated with lower impulse control at 24 months of age, and mediated the association between higher maternal interleukin-6 concentrations and lower impulse control. These findings provide new evidence in humans linking maternal inflammation during pregnancy with newborn brain and emerging behavioral phenotypes relevant for psychiatric disorders. A better understanding of intrauterine conditions that influence offspring disease susceptibility is warranted to inform targeted early intervention and prevention efforts. Copyright © 2017 Society of Biological Psychiatry

  2. Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes

    DEFF Research Database (Denmark)

    Hamid, Y H; Rose, C S; Urhammer, S A

    2005-01-01

    The cytokine interleukin 6 (IL-6) is an essential regulator of the acute phase response associated with insulin-resistant states including type 2 diabetes and obesity. Three polymorphisms at positions -597, -572, and -174 of the IL6 promoter have been reported to influence IL6 transcription. The ....... The aim of this study was to investigate whether the IL6 promoter polymorphisms were associated with features of the WHO-defined metabolic syndrome and related quantitative traits in 7,553 Caucasian Danes....

  3. Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats

    Science.gov (United States)

    Mohammadi, Shima; Karimzadeh Bardei, Latifeh; Hojati, Vida; Ghorbani, Azita; Nabiuni, Mohammad

    2017-01-01

    Objective Curcumin protects the liver against injury and fibrosis through suppressing hepatic inflammation, attenuating hepatic oxidative stress (OS), and inhibiting hepatic stellate cells (HSCs) activation. Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are considered as common metabolic disorders. Low-grade chronic inflammation with different markers, such as elevated C-reactive protein (CRP) and interleukin-6 (IL-6) levels, play a crucial role in PCOS. This study aimed to evaluate the therapeutic effects of curcumin on IL-6 and CRP levels as well as insulin resistance (IR) index on liver function in PCOS rats. Materials and Methods In this experimental study, 90 adult Wistar rats were divided into control (n=18), sham (n=18), PCOS (n=18) and curcumin-treated PCOS groups (n=36). PCOS group was injected subcutaneously with 2 mg estradio-valerate (E2V). After 60 days, PCOS group was treated with curcumin [100 and 300 mg/kg body weight (BW)] for 14 days and anesthetized by chloroform. Blood and liver samples were collected for histological and serological analyses. Data were analyzed using In-Stat 3 via one-way analysis of variance (ANOVA). Results Histological and serological analyses showed a reduction in number of necrotic cells, IR index, as well as IL-6 and CRP levels in PCOS rats that were treated with various concentrations of curcumin. Conclusion In this study, curcumin decreased liver inflammation by induction of insulin sensitivity and reduction of hepatic necrosis. Therefore, curcumin may be considered as protective factor against inflammatory state of PCOS. PMID:28836404

  4. Synthesis of interleukin 6 (interferon-. beta. /sub 2//B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    Energy Technology Data Exchange (ETDEWEB)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-05-05

    Interleukin 6 (IL-6; also referred to as interferon-..beta../sub 2/, 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1.

  5. Synthesis of interleukin 6 (interferon-β2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    International Nuclear Information System (INIS)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-01-01

    Interleukin 6 (IL-6; also referred to as interferon-β 2 , 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1

  6. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Berg, E.A. van den; Fiers, W.; Dooijewaard, G.

    1990-01-01

    Endothelial cells play an important role in the regulation of fibrinolysis by the production of several key regulatory proteins. The cytokines tumor necrosis factor (TNF), lymphotoxin, and interleukin-1 (IL-1), but not interleukin-6, increase the production of plasminogen activator inhibitor-1

  7. The Link Between Oxidative Stress Response and Tumor Necrosis ...