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

Ding, Jianwen; Su, Shujun; You, Tao; Xia, Tingting; Lin, Xiang; Chen, Zhaocong; Zhang, Liqun

doi:10.6061/clinics/2020/e1801

Cited by 45 publications

(29 citation statements)

References 56 publications

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“…Evidence showed an imbalance in Th1/Th2 and other cell subpopulations in patients with SLE, which significantly increased the levels of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β ( 86 ). IL-6 and IL-1β were known to drive Th17 differentiation and promote the levels of serum IL-21 and IL-17 which correlated with disease activity ( 87 , 88 ). When MSCs exposed to IL-6, the stemness of MSCs was enhanced through an ERK1/2-dependent mechanism ( 89 ); however, whether IL-6 could reduce the immunosuppressive function of MSCs still unclear.…”

Section: Potential Causes Of Msc Therapy Inefficacy In Sle Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus

Guo

Pan

et al. 2021

Front. Immunol.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the immune system, including B cells, T cells, and dendritic cells, etc., the mechanisms underlying SLE pathogenesis remain unclear. Therefore, effective and low side-effect therapies for SLE are lacking. Recently, mesenchymal stem cell (MSC) therapy for autoimmune diseases, particularly SLE, has gained increasing attention. This therapy can improve the signs and symptoms of refractory SLE by promoting the proliferation of Th2 and Treg cells and inhibiting the activity of Th1, Th17, and B cells, etc. However, MSC therapy is also reported ineffective in some patients with SLE, which may be related to MSC- or patient-derived factors. Therefore, the therapeutic effects of MSCs should be further confirmed. This review summarizes the status of MSC therapy in refractory SLE treatment and potential reasons for the ineffectiveness of MSC therapy from three perspectives. We propose various MSC modification methods that may be beneficial in enhancing the immunosuppression of MSCs in SLE. However, their safety and protective effects in patients with SLE still need to be confirmed by further experimental and clinical evidence.

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Section: Potential Causes Of Msc Therapy Inefficacy In Sle Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus

Guo

Pan

et al. 2021

Front. Immunol.

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“…Due to the lack of a pericytes cell line, we utilized 10T1/2 cells of mesenchymal stem cell origin, which are widely used for studying pericyte biology in various organs including kidney (47–49). As an increase in IL-6 has been reported in the pathogenesis of kidney disease, (50–52) we explored its function in STAT3 mediated proliferation, migration, and induction of fibrotic signaling in 10T1/2 cells. We found that pSTAT3 is increased and translocated to the nucleus after IL-6 treatment, and this was inhibited by stattic, a specific inhibitor of STAT3, indicating that these cells responded to IL-6 ( Figure 4A, B, C and D ).…”

Section: Resultsmentioning

confidence: 99%

Stromal-cell deletion of STAT3 protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration

Ajay

Zhao

Vig

et al. 2021

Preprint

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Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor implicated in the pathogenesis of kidney fibrosis. Although tubular Stat3 deletion in tubular epithelial cells is known to protect mice from kidney fibrosis, the exact function of STAT3 in stromal cells remains unknown. We utilized stromal-cell Stat3 knock-out (KO) mice, CRISPR and pharmacologic activators and inhibitors of STAT3 to investigate its function in pericyte-like cells. STAT3 is phosphorylated in tubular epithelial cells in acute kidney injury whereas its activation expanded to interstitial cells in chronic kidney disease in mice and humans. Stromal cell-specific deletion of Stat3 protects mice from folic acid- and aristolochic acid-induced kidney fibrosis. Mechanistically, STAT3 directly regulates the inflammatory pathway, differentiation of pericytes into myofibroblasts. Specifically, STAT3 activation leads to an increase in migration and profibrotic signaling in genome-edited pericyte-like cells, 10T1/2. Conversely, Stat3 KO or blocking STAT3 function inhibits detachment, spreading, migration, and profibrotic signaling. Furthermore, STAT3 binds to Collagen1a1 promoter of fibrotic mouse kidneys and in pericyte-like cells. Together, our study identifies a previously unknown function of STAT3 in stromal cells that promotes kidney fibrosis and may have therapeutic value in fibrotic kidney disease.

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“…Recently it was shown that also in patients with SLE the IL-6 expression correlates with disease activity [ 34 ]. Comparatively, therapy with tocilizumab, an anti-human IL-6 receptor antibody, did not show the hoped-for therapeutic success in the case of SLE [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation

Marczynski

Meineck

Xia

et al. 2021

IJMS

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Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6−/− MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.

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

Cited by 45 publications

References 56 publications

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus

Stromal-cell deletion of STAT3 protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration

Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation

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