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      International Journal of COPD (submit here)

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      Increased serum IL-17 and decreased serum IL-10 and IL-35 levels correlate with the progression of COPD

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          Abstract

          Purpose

          This study aimed to measure the serum levels of interleukin (IL)-17, IL-10, and IL-35 in patients with stable chronic obstructive pulmonary disease (COPD) and disclose the correlations between their expression levels and clinical factors of patients.

          Methods

          A total of 75 patients with stable COPD (47 males and 28 females) and 30 healthy controls (15 males and 15 females) were included in this study. The serum levels of IL-17, IL-10, and IL-35 were determined by enzyme-linked immunosorbent assay. The correlations between their expression levels and clinical factors of patients were determined using linear regression methods.

          Results

          The serum level of IL-17 was upregulated in stable COPD, and increased IL-17 expression was positively correlated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, modified Medical Research Council (mMRC) score, and long clinical history ( P<0.05), but negatively correlated with the pulmonary function ( P<0.05) of patients. The serum levels of IL-10 and IL-35 were downregulated in stable COPD, and decreased IL-10 and IL-35 levels negatively correlated with the smoking status, GOLD grading, mMRC score, and long clinical history ( P<0.05), but positively correlated with the pulmonary function ( P<0.05) of patients. Moreover, the level of IL-17 negatively correlated with IL-10 and IL-35, but IL-10 positively correlated with IL-35.

          Conclusion

          The serum levels of IL-17, IL-10, and IL-35 correlated with the clinical factors of COPD, indicating that they can serve as indicators to estimate the progression of COPD.

          Most cited references26

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          The inhibitory cytokine IL-35 contributes to regulatory T-cell function.

          Regulatory T (T(reg)) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease, and for regulating homeostatic lymphocyte expansion. However, they also suppress natural immune responses to parasites and viruses as well as anti-tumour immunity induced by therapeutic vaccines. Although the manipulation of T(reg) function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27beta) and interleukin-12 alpha (Il12a, which encodes IL-12alpha/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) T(reg) cells but not by resting or activated effector CD4+ T (T(eff)) cells, and that an Ebi3-IL-12alpha heterodimer is constitutively secreted by T(reg) but not T(eff) cells. Both Ebi3 and Il12a messenger RNA are markedly upregulated in T(reg) cells co-cultured with T(eff) cells, thereby boosting Ebi3 and IL-12alpha production in trans. T(reg)-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for T(reg)-cell development and function. Ebi3-/- and Il12a-/- T(reg) cells have significantly reduced regulatory activity in vitro and fail to control homeostatic proliferation and to cure inflammatory bowel disease in vivo. Because these phenotypic characteristics are distinct from those of other IL-12 family members, this novel Ebi3-IL-12alpha heterodimeric cytokine has been designated interleukin-35 (IL-35). Ectopic expression of IL-35 confers regulatory activity on naive T cells, whereas recombinant IL-35 suppresses T-cell proliferation. Taken together, these data identify IL-35 as a novel inhibitory cytokine that may be specifically produced by T(reg) cells and is required for maximal suppressive activity.
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            IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis.

            IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17(-/-) murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17(-/-) mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17(-/-) mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17(-/-) CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-gamma(-/-) cells, while IFN-gamma-producing cells were increased in IL-17(-/-) cells, suggesting that IL-17 and IFN-gamma mutually regulate IFN-gamma and IL-17 production. These observations indicate that IL-17 rather than IFN-gamma plays a crucial role in the development of EAE.
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              Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary.

              This Executive Summary of the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: (i) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (ii) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; (iii) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; (iv)non-pharmacological therapies are comprehensively presented and (v) the importance of co-morbid conditions in managing COPD is reviewed.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2018
                20 August 2018
                : 13
                : 2483-2494
                Affiliations
                [1 ]Department of Respiratory Medicine, Affiliated Hospital, Qingdao University, Qingdao, China, czzresearch8866@ 123456126.com
                [2 ]Department of Respiratory Medicine, Affiliated Hospital of Jining Medical University, Jining, China
                Author notes
                Correspondence: Zhaozhong Cheng, Department of Respiratory Medicine, Affiliated Hospital, Qingdao University, 59 Haier Road, Qingdao 266021, China, Email czzresearch8866@ 123456126.com
                Article
                copd-13-2483
                10.2147/COPD.S167192
                6108328
                30154651
                7aa0223f-4205-492f-b6ab-498a7d2eab9f
                © 2018 Jiang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Respiratory medicine
                chronic obstructive pulmonary disease,interleukin-17,interleukin-10,interleukin-35,serum

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