Home / Journals / ECN / Vol.21, No.4, 2010
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  • Open AccessOpen Access

    REVIEW

    Treatment failure with antagonists of TNF-α: mechanisms and implications for the care of patients

    Marine Desroches, Gauthier Louis, Aude Gleizes, Roman Krzysiek, Dominique Emilie
    European Cytokine Network, Vol.21, No.4, pp. 226-231, 2010, DOI:10.1684/ecn.2010.0212
    Abstract The use of TNF-α antagonists has substantially improved the care of many patients with inflam-matory and autoimmune diseases. However, approximately one third of such patients fail to respond well totreatment, regardless of the antagonist used or of the underlying disease. The mechanisms underlying these fail-ures are analyzed in this review, and proposals made concerning how best to adapt therapeutic decisions inthese instances. More >

  • Open AccessOpen Access

    ARTICLE

    Distinct cytokine profiles define clinical immune response to falciparum malaria in regions of high or low disease transmission

    Swapnil Sinha1, Tabish Qidwai1, Kanika Kanchan1, Ganga N. Jha1, Prerna Anand2, Sudhanshu S. Pati3, Sanjib Mohanty3, Saroj K. Mishra3, Prajesh K. Tyagi4, Surya K. Sharma4, Shally Awasthi2, Vimala Venkatesh2, Saman Habib1
    European Cytokine Network, Vol.21, No.4, pp. 232-240, 2010, DOI:10.1684/ecn.2010.0208
    Abstract The immune effector response to Plasmodium falciparum infection involves a finely-tuned inter-play between different cell types and cytokines. However, the processes by which they mediate the development of clinical immunity, in areas of different endemicity, are poorly understood. We analyzed circulating levels of pro-inflammatory (TNF, IFN-γ, IL-12, IL-16) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines in control and patient groups drawn from a P. falciparum-endemic and a non-endemic region of India. The endemic region control population exhibited a lower pro- to anti-inflammatory cytokine ratio, indicating a shift towards a high basal Th2 response. Levels of IL-10 contributed most… More >

  • Open AccessOpen Access

    ARTICLE

    Relationship between IL-6/ERK and NF-κB: a study in normal and pathological human prostate gland

    Gonzalo Rodríguez-Berriguete1, Angela Prieto1, Benito Fraile1, Yosra Bouraoui4, Fermín R. de Bethencourt3, Pilar Martínez-Onsurbe2, Gabriel Olmedilla2, Ricardo Paniagua1, Mar Royuela1
    European Cytokine Network, Vol.21, No.4, pp. 241-250, 2010, DOI:10.1684/ecn.2010.0211
    Abstract Background. There is growing evidence that inflammation is a causal factor in cancer, wherepro-inflammatory cytokines such as IL-6, IL-1 or TNF-α could induce cellular proliferation by activation ofNF-κB. This study focuses on the IL-6/ERK transduction pathway, its relationship with NF-κB, and the conse-quences of dysregulation in the development of prostate pathologies such as benign prostate hyperplasia (BPH),prostate intraepithelial neoplasia (PIN) and prostate cancer (PC). Methods. Immunohistochemical and Westernblot analyses for IL-6, gp-130, Raf-1, MEK-1, ERK-1, p-MEK, ERK-2, p-ERK, NF-κB/p-50 and NF-κB/p-65were carried out in 20 samples of normal prostate glands, 35 samples of BPH, 27… More >

  • Open AccessOpen Access

    ARTICLE

    Serum cytokine levels as putative prognostic markers in the progression of chronic HCV hepatitis to cirrhosis

    Susan Costantini1, Francesca Capone1, Eliana Guerriero1, Patrizia Maio2, Giovanni Colonna3, Giuseppe Castello1
    European Cytokine Network, Vol.21, No.4, pp. 251-256, 2010, DOI:10.1684/ecn.2010.0214
    Abstract Hepatitis C virus (HCV) infection can present as an acute manifestation, and can lead to severecomplications such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). It represents a globalhealth problem because there is no vaccine currently available. Cytokines play an important role in viralclearance, infection control, inflammation, regeneration and fibrosis, and also are implicated in the pathologicalprocesses occurring in the liver during viral infection. Immunological markers of chronic HCV hepatitis pro-gression as compared to cirrhosis and HCC would be extremely useful, particularly for distinguishing betweenthe molecules produced during HCV-induced chronic inflammation and those secreted during… More >

  • Open AccessOpen Access

    ARTICLE

    Effect of omeprazole on the concentration of interleukin-6 and transforming growth factor-β1 in patients receiving dual antiplatelet therapy after percutaneous coronary intervention

    Bartosz Hudzik1, Janusz Szkodzinski1, Aleksander Danikiewicz2, Krzysztof Wilczek1, Wojciech Romanowski2, Andrzej Lekston1, Lech Polonski1, Barbara Zubelewicz-Szkodzinska2
    European Cytokine Network, Vol.21, No.4, pp. 257-263, 2010, DOI:10.1684/ecn.2010.0213
    Abstract Background. Dual antiplatelet therapy (aspirin plus clopidogrel) is recommended in patients undergoing percutaneous coronary intervention (PCI). Treatment with proton pump inhibitors (PPIs) decreases bleeding rate. Alarming reports have been made that PPIs may decrease the antiplatelet activity of clopidogrel. We sought to determine whether levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) might help distinguish individuals at risk for adverse events. Methods. Thirty-eight patients on aspirin and clopidogrel were enrolled and divided into two groups: group 1 [patients receiving omeprazole (n = 18)] and group 2 [patients not receiving omeprazole (n = 20)]. Patients… More >

  • Open AccessOpen Access

    ARTICLE

    Serum and urinary levels of IL-18 and its inhibitor IL-18BP in systemic lupus erythematosus

    Paola Migliorini1, Consuelo Anzilotti1, Federico Pratesi1, Paola Quattroni2, Marco Bargagna2, Charles A. Dinarello3, Diana Boraschi2
    European Cytokine Network, Vol.21, No.4, pp. 264-271, 2010, DOI:10.1684/ecn.2010.0210
    Abstract Overproduction of inflammation-related cytokines plays an important role in systemic lupuserythematosus (SLE). A crucial cytokine is IL-18, a member of the IL-1 family involved in the regulation ofboth innate and acquired immune responses. The aim of this study was to evaluate free IL-18 levels in theserum and urine of SLE patients, in order to establish their relationship with other biomarkers of disease activ-ity. Serum and urine levels of IL-18 and IL-18BP were measured by ELISA in 50 SLE patients and in32 healthy subjects; free IL-18 was calculated using the law of mass action. Serum levels… More >

  • Open AccessOpen Access

    ARTICLE

    Impact of treatment with metformin on adipokines in patients with polycystic ovary syndrome

    İlhan Tarkun1, Emre Dikmen2, Berrin Çetinarslan1, Zeynep Cantürk1
    European Cytokine Network, Vol.21, No.4, pp. 272-277, 2010, DOI:10.1684/ecn.2010.0217
    Abstract Background. Adipose tissue synthesizes various adipokines such as resistin, adiponectin and visfa-tin, which have an effect on insulin resistance. This study was designed to show the effect of metformin, one of the most important drugs used to reduce insulin resistance in patients with polycystic ovary syndrome (PCOS), on these adipokines. Methods. The study group consisted of 24 women with PCOS and 25 healthy, age- and weight-matched, normally menstruating women. Hormone and lipid profiles, visfatin, adiponectin and resistin were measured in all cases, before and after metformin treatment. Results. Serum visfatin levels were found to be… More >

  • Open AccessOpen Access

    ARTICLE

    Changes in cytokine concentrations following successful ablation of atrial fibrillation

    Pavel Osmancik1, Zdenek Peroutka1, Petr Budera2, Dalibor Herman1, Petr Stros1, Zbynek Straka2
    European Cytokine Network, Vol.21, No.4, pp. 278-284, 2010, DOI:10.1684/ecn.2010.0216
    Abstract Aims. Atrial fibrillation is associated with the activation of inflammatory processes [e.g. higher concentrations of pro-inflammatory cytokines interleukin-6 (IL-6), C-reactive protein (CRP)], as well as a pro-thrombotic state [e.g. increased concentration of serum pro-thrombotic markers P-selectin and CD40 ligand (CD40L)]. The aim of the present study was to establish, whether successful epicardial ablation of AF leads to decreased concentrations of traditional inflammatory and thrombotic markers. Methods. Twenty-five patients with symptomatic paroxysmal or persistent AF were prospectively studied. All underwent epicardial isolation of pulmonary veins. The success of the ablation was assessed clinically and with three… More >

  • Open AccessOpen Access

    ARTICLE

    Identification of specific tumor necrosis factor-α-susceptible and -protective haplotypes associated with the risk of type 1 diabetes

    Mouna Stayoussef1, Jihen Benmansour1, Fayza A. Al-Jenaidi2,3, Mansoor H. Rajab2, Hichem B. Said4, Mohamed Ourtani5, Chiheb B. Rayana1, Touhami Mahjoub1, Wassim Y. Almawi3
    European Cytokine Network, Vol.21, No.4, pp. 285-291, 2010, DOI:10.1684/ecn.2010.0215
    Abstract Aim. We investigated the association of tumor necrosis factor (TNF)α gene polymorphism with type 1 diabetes (T1D). Methods. TNF-α -1031T/C, -863C/A, -857C/T, -376G/A, -308G/A, -238G/A, and +488G/A single nucleotide polymorphisms (SNPs) were assessed in 198 T1DM patients and 180 age-and gender-matched, normoglycemic control subjects using PCR-restriction fragment length polymorphism (RFLP). Results. Higher frequencies of -863A (p = 8.0 × 10-6 ), -857T (p = 1.4 × 10-4 ), and -238A (p = 0.002) alleles were seen in T1D patients than in the control group. Significant differences were noted in the distribution of -863T/C, -857C/T, -376G/A, -308G/A,… More >

  • Open AccessOpen Access

    ARTICLE

    Proinflammatory cytokine gene polymorphisms in Behcet’s disease

    Aliakbar Amirzargar1,2, Farhad Shahram3,4, Enayat Nikoopour1, Nima Rezaei1,2, Keyvan Saeedfar3, Naghmeh Ziaei3, Fereydoun Davatchi3,4
    European Cytokine Network, Vol.21, No.4, pp. 292-296, 2010, DOI:10.1684/ecn.2009.0209
    Abstract Behçet’s disease (BD) is a chronic, systemic disease, characterized by oral and genital lesions, andocular inflammation. There is evidence indicating altered levels of proinflammatory cytokines, such as interleukin(IL)-6 and tumor necrosis factor alpha (TNF-α) in patients with BD. This study involved 150 patients with BD and140 healthy controls, and investigated the role of proinflammatory cytokine gene polymorphisms in the disease. Thefrequency of the TNF-α (-238) G/G genotype was significantly higher in the patient group, compared to the controls(p < 0.001), whilst the G/A genotype was significantly lower in the patients with BD (p < 0.001). More >

  • Open AccessOpen Access

    ARTICLE

    Different dynamics of IL-15R activation following IL-15 cis- or trans-presentation

    Harmonie Perdreau1,2, Erwan Mortier1,2, Grégory Bouchaud1,2, Véronique Solé1,2, Yvan Boublik3, Ariane Plet1,2,*, Yannick Jacques1,2,*
    European Cytokine Network, Vol.21, No.4, pp. 297-307, 2010, DOI:10.1684/ecn.2010.0207
    Abstract Interleukin (IL)-15 is a cytokine critical for the homeostasis and the function of NK cells, NK-Tcells, and memory CD8+ T cells. IL-15 signals are delivered through the IL-15Rβ and the commonγ (γc) receptorchains. The third receptor chain, IL-15Rα, confers specificity and high affinity for the cytokine. While IL-15 canactivate with high affinity the trimeric receptor expressed by a target cell (cis-presentation), IL-15Rα is alsoknown to trans-present IL-15 with high affinity to target cells expressing the IL-15Rβ/γc complex. In order tocompare the IL-15 cis- and trans-presentation processes, and using a T cell line expressing both IL-15Rα/β/γc andIL-15Rβ/γc, we analyzed cell… More >

  • Open AccessOpen Access

    ARTICLE

    Tissue-specific expression of IL-15RA alternative splicing transcripts and its regulation by DNA methylation

    Susana N. Diniz1,2, Karen P. T. Pendeloski1, Andrey Morgun1,3, Iouri Chepelev4, Maria Gerbase-DeLima1,*, Natalia Shulzhenko1,3,*
    European Cytokine Network, Vol.21, No.4, pp. 308-318, 2010, DOI:10.1684/ecn.2010.0218
    Abstract The human IL-15RA gene encoding the alpha chain of the IL-15 receptor is expressed in a varietyof immune and non-immune cell types from different tissues, and generates multiple splicing events of func-tional importance. We aimed to evaluate expression of IL-15RA transcripts generated by alternative usage oftranscription start site (Var1 and Var2) and by deletion of exon 3 (Del3), exon 2 (Del2), or both (Del2,3) in dif-ferent human tissues. Since a CpG island was found near to the IL-15RA gene transcription start site, we alsoinvestigated the role of DNA methylation on the expression of IL-15RA full-length… More >

  • Open AccessOpen Access

    ARTICLE

    Role of mitogen-activated protein kinase and PI3K pathways in the regulation of IL-12-family cytokines in dendritic cells and the generation of TH-responses

    Andrew M. Jackson1,*, Lori A. Mulcahy1,*, Joanne Porte2, Hester A. Franks1, Mohamed El Refaee1, Qunwei Wang1, Suharsh Shah1, XingWu Zhu1, Poulam M. Patel1
    European Cytokine Network, Vol.21, No.4, pp. 319-328, 2010, DOI:10.1684/ecn.2010.0219
    Abstract Mitogen-activated protein kinases (MAPK) are targets for the immune-modulation of dendriticcells (DC). However, our knowledge of their role in the regulation of IL-12-family cytokines is limited. Thisstudy investigated the roles of p38, JNK, p44/42 and PI3K pathways in IL-12/23/27 production by human DC,and their impact on naïve TH-responses. We first identified TOP and UBC as robust DC housekeeping genes.Peak transcription of p35 and p40 occurred by 12h, p19 and p28 by 8h and EBI3 by 12-24h. Using selectiveantagonists, we showed that p38 was a positive regulator of IL-12, 23 and 27, JNK positively regulated IL-12and… More >

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