Changes of Serum IL-6, IL-17, and Complements in Systemic Lupus Erythematosus Patients

Tang, Yamei; Tao, Huai; Gong, Yuji; Chen, Fang; Li, Cunyan; Yang, Xiudeng

doi:10.1089/jir.2018.0169

Cited by 30 publications

(27 citation statements)

References 29 publications

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“…The serum IL-6 levels ranged from 4.272±0.4222 to 123.71±81.783 (pg/mL) in SLE patients and 0.93 ± 0.95 to 10.46 ± 4.33 (pg/mL) in healthy controls. A total of 13 studies compared the serum IL-6 levels between SLE patients and healthy controls (23)(24)(25)(27)(28)(29)(32)(33)(34)39,40,43,46). Serum IL-6 levels between active and inactive SLE patients were compared in 9 studies (24)(25)(26)29,31,39,(41)(42)(43).…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

“…A total of 13 studies compared the serum IL-6 levels between SLE patients and healthy controls (23)(24)(25)(27)(28)(29)(32)(33)(34)39,40,43,46). Serum IL-6 levels between active and inactive SLE patients were compared in 9 studies (24)(25)(26)29,31,39,(41)(42)(43). Additionally, the correlation coefficient between serum IL-6 level and SLE disease activity was reported in 13 studies (24)(25)(26)(29)(30)(31)(35)(36)(37)(38)(39)44,45).…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

“…Additionally, the correlation coefficient between serum IL-6 level and SLE disease activity was reported in 13 studies (24)(25)(26)(29)(30)(31)(35)(36)(37)(38)(39)44,45). Among all included studies, 3 studies focused on children with SLE (25,28,46), and 21 studies focused on adults with SLE (23,24,26,27,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). The NOS scores for the included studies ranged from six to seven, indicating that they were of moderate to high quality and suitable for pooled analysis.…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

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

Ding¹,

Su²,

You³

et al. 2020

Clinics

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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, po0.01) 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 Index44 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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Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

See 1 more Smart Citation

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

Ding¹,

Su²,

You³

et al. 2020

Clinics

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“…Herein, we also demonstrate that cytokines, previously shown to be increased in the serum or tissue of patients with SLE, strongly enhance the type III IFN production by healthy pDCs. These cytokines include IFN-α [35], GM-CSF [21,36,37], IL-6 [38,39], and IL-3 [40][41][42], but also type III IFN itself [6,43]. Furthermore, all type III IFN subtypes enhanced the IFN-α production.…”

Section: Discussionmentioning

confidence: 99%

The regulation and pharmacological modulation of immune complex induced type III IFN production by plasmacytoid dendritic cells

et al. 2020

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Objective: Patients with systemic lupus erythematosus (SLE) have an ongoing interferon (IFN) production due to an activation of plasmacytoid dendritic cells (pDCs), which can be triggered to type I IFN synthesis by RNA containing immune complexes (RNA-IC). Considering emerging data suggesting a role of type III IFN in the SLE disease process, we asked if RNA-IC can induce type III IFN production in pDC and how this production can be regulated. Methods: Peripheral blood mononuclear cells (PBMCs) or immune cell subsets were isolated from healthy blood donors or SLE patients and stimulated with IC containing U1 snRNP and SLE-IgG (RNA-IC). Hydroxychloroquine (HCQ) and an interleukin receptor 1-associated kinase 4 inhibitor (IRAK4i) were added to cell cultures. Cytokine mRNA levels were determined with a microarray and protein levels with immunoassays. Single-cell RNA sequencing of pDCs using ddSEQ technology was performed. Results: Type III IFN mRNA and protein was induced in RNA-IC-stimulated pDC-NK and pDC-B cell co-cultures. A subset of activated pDCs (3%) expressed both type III and type I IFN mRNA. IFN-λ2, IFN-α2b, interleukin (IL)-3, IL-6, or granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced IFN-λ1/3 production 2-5-fold. HCQ and an IRAK4i blocked the RNA-IC-triggered IFN-λ1/3 production (p < 0.01). IFN-α2b and GM-CSF increased the proportion of SLE patients producing IFN-λ1/3 in response to RNA-IC from 11 to 33%. Conclusions: Type III IFN production is triggered by RNA-IC in pDCs in a TLR-MyD88-dependent manner, enhanced by NK and B cells as well as several pro-inflammatory cytokines. These results support a contributing role for both type I and type III IFNs in SLE, which needs to be considered when targeting the IFN system in this disease.

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“…IL-6 is an important inflammatory factor that not only increases rapidly in the acute inflammatory response but also significantly up-regulates the immune response in immune diseases ( 67 , 68 ). The increase in serum IL-6 levels is positively correlated with the disease activity of SLE ( 69 ). There is also a positive correlation with IL-17, which is why there have been studies on the bispecific antibody (BsAbs) of both factors.…”

Section: Targeting Cytokinesmentioning

confidence: 99%

A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target

Yang

Zhao

et al. 2020

Front. Immunol.

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Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple immune cells. Due to its complex pathogenesis, the effectiveness of traditional treatment methods is limited. Many patients have developed resistance to conventional treatment or are not sensitive to steroid and immunosuppressant therapy, and so emerging therapeutic antibodies have become an alternative and have been shown to work well in many patients with moderate and severe SLE. This review summarizes the biological agents that are in the preclinical and clinical trial study of SLE. In addition to the various monoclonal antibodies that have been studied for a long time, such as belimumab and rituximab, we focused on another treatment for SLE, bispecific antibodies (BsAbs) such as tibulizumab, which simultaneously targets multiple pathogenic cytokines or pathways. Although the application of BsAbs in cancer has been intensively studied, their application in autoimmune diseases is still in the infant stage. This unique combined mechanism of action may provide a novel therapeutic strategy for SLE.

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Changes of Serum IL-6, IL-17, and Complements in Systemic Lupus Erythematosus Patients

Cited by 30 publications

References 29 publications

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

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

The regulation and pharmacological modulation of immune complex induced type III IFN production by plasmacytoid dendritic cells

A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target

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