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      Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis

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          Abstract

          Interleukin-6 (IL-6) plays a crucial role in systemic autoimmunity and pathologic inflammation. Numerous studies have explored serum IL-6 levels in systemic lupus erythematosus (SLE) and their correlation with disease activity. Here, we performed a meta-analysis to quantitatively assess the correlation between the serum IL-6 levels and SLE activity.

          The PubMed and EMBASE databases were thoroughly searched for relevant studies up to September 2019. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were used to describe the differences between serum IL-6 levels in SLE patients and healthy controls and between those in active SLE patients and inactive SLE patients. The correlation between the serum IL-6 levels and disease activity was evaluated using Fisher’s z values.

          A total of 24 studies involving 1817 SLE patients and 874 healthy controls were included in this meta-analysis. Serum IL-6 levels were significantly higher in SLE patients than in the healthy controls (pooled SMD: 2.12, 95% CI: 1.21-3.03, Active SLE patients had higher serum IL-6 levels than inactive SLE patients (pooled SMD: 2.12, 95% CI: 1.21-3.03). Furthermore, the pooled Fisher’s z values (pooled Fisher’s z=0.36, 95% CI: 0.26-0.46, p<0.01) showed that there was a positive correlation between the serum IL-6 levels and SLE activity.

          This study suggested that serum IL-6 levels were higher in patients with SLE than in healthy controls, and they were positively correlated with disease activity when Systemic Lupus Erythematosus Disease Activity Index>4 was defined as active SLE. More homogeneous studies with large sample sizes are warranted to confirm our findings due to several limitations in our meta-analysis.

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          Frequency Distribution of the Values of the Correlation Coefficient in Samples from an Indefinitely Large Population

          R Fisher (1915)
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            Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells.

            Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) have been linked to host defense and autoimmune diseases. In mice, the differentiation of T(H)-17 cells requires transforming growth factor-beta and IL-6 and the transcription factor RORgammat. We report here that for human naive CD4(+) T cells, RORgammat expression and T(H)-17 polarization were induced by IL-1beta and enhanced by IL-6 but were suppressed by transforming growth factor-beta and IL-12. Monocytes and conventional dendritic cells, but not monocyte-derived dendritic cells activated by microbial stimuli, efficiently induced T(H)-17 priming, and this function correlated with antigen-presenting cell production of IL-1beta and IL-6 but not IL-12. Our results identify cytokines, antigen-presenting cells and microbial products that promote the polarization of human T(H)-17 cells and emphasize an important difference in the requirements for the differentiation of T(H)-17 cells in humans and mice.
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              Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity.

              Imbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity. Sixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA). SLE patients were found to have significantly higher levels of IL-17 (p<0.001), IL-6 (p<0.01), IL-12 (p<0.001) and IL-10 (p<0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p<0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p<0.01), IL-6 (p<0.05), IL-17 (p<0.001), IL-23 (p<0.01) and TGF-β (p<0.5) and lower IFN-γ (p<0.001) and IL-10 (p<0.01) than those of healthy subjects. Our study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Clinics (Sao Paulo)
                Clinics (Sao Paulo)
                clin
                Clinics
                Faculdade de Medicina / USP
                1807-5932
                1980-5322
                05 October 2020
                2020
                : 75
                : e1801
                Affiliations
                [I ]Department of Kidney Disease, Lanzhou University Second Hospital, Lanzhou 730030, China
                [II ]Department of Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
                [III ]Department of Endocrinology and Rheumatology, Affiliated Southeast Hospital of Xiamen University/909th Hospital of People's Liberation Army, 269 Zhanghua Middle Road, Zhangzhou, 363000, Fujian Province, China
                [IV ]Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou city, Guangdong Province, China
                [V ]Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China
                Author notes

                #Contributed equally to this work

                Author information
                https://orcid.org/0000-0002-4679-6732
                https://orcid.org/0000-0002-5133-3820
                https://orcid.org/0000-0003-3256-7258
                https://orcid.org/0000-0001-5145-9506
                https://orcid.org/0000-0001-9117-5495
                https://orcid.org/0000-0002-0144-2754
                https://orcid.org/0000-0003-1452-203X
                Article
                cln_75p1
                10.6061/clinics/2020/e1801
                7536892
                33084768
                e477552e-c77b-4a59-8281-2e68b45efd44
                Copyright © 2020 CLINICS

                This is an Open Access article distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

                History
                : 22 February 2020
                : 8 June 2020
                Categories
                Review Article

                Medicine
                interleukin-6,systemic lupus erythematosus,autoimmune disease
                Medicine
                interleukin-6, systemic lupus erythematosus, autoimmune disease

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