IL‐38: A novel cytokine in systemic lupus erythematosus pathogenesis

Xu, Wang‐Dong; Su, Lin‐Chong; Liu, Xiaoyan; Wang, Jiamin; Yuan, Zhi‐Chao; Qin, Zhen; Zhou, Xian‐Liang; Huang, An‐Fang

doi:10.1111/jcmm.15737

Cited by 25 publications

(21 citation statements)

References 39 publications

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“…The levels of this cytokine were higher in active patients and associated with multiple clinical and laboratory parameters including arthritis, pericarditis, haematuria, proteinuria, pyuria and anti-dsDNA. Correlation analysis indicated that plasma IL-38 correlated positively with SLEDAI and negatively with C3 and C4 levels [ 88 ].…”

Section: Il-1 Il-18 and Il-38mentioning

confidence: 99%

Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

Idborg

Oke

2021

IJMS

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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease. The disease is characterized by activation and dysregulation of both the innate and the adaptive immune systems. The autoimmune response targets self-molecules including cell nuclei, double stranded DNA and other intra and extracellular structures. Multiple susceptibility genes within the immune system have been identified, as well as disturbances in different immune pathways. SLE may affect different organs and organ systems, and organ involvement is diverse among individuals. A universal understanding of pathophysiological mechanism of the disease, as well as directed therapies, are still missing. Cytokines are immunomodulating molecules produced by cells of the immune system. Interferons (IFNs) are a broad group of cytokines, primarily produced by the innate immune system. The IFN system has been observed to be dysregulated in SLE, and therefore IFNs have been extensively studied with a hope to understand the disease mechanisms and identify novel targeted therapies. In several autoimmune diseases identification and subsequent blockade of specific cytokines has led to successful therapies, for example tumor necrosis factor-alpha (TNF-α) inhibition in rheumatoid arthritis. Authors of this review have sought corresponding developments in SLE. In the current review, we cover the actual knowledge on IFNs and other studied cytokines as biomarkers and treatment targets in SLE.

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Section: Il-1 Il-18 and Il-38mentioning

confidence: 99%

Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

Idborg

Oke

2021

IJMS

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“…IL-38 has been considered as an IL-1 family antagonist for its high homology to IL-36Ra and IL-1Ra [ 10 ]. Most studies conclude that IL-38 exerts anti-inflammatory effects in several autoimmune diseases, including RA, AA, and SLE [ 13 – 15 ]. On the contrary, several other studies have shown that IL-38 can act as a pro-inflammatory factor, and it can modestly enhance candida-induced IL-22 and IL-17 expression in human PBMCs at a higher concentration [ 12 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…IL-38 is an abundant, ubiquitously expressed cytokine, which can be secreted by fibroblast-like synoviocytes, peripheral blood mononuclear cells (PBMCs), keratinocytes, epithelial cells, and various immune cells, such as B cells, natural killer (NK) cells, macrophages, and dendritic cells (DCs) [ 11 , 12 ]. Abnormal expression of IL-38 has been found in many inflammatory diseases, including rheumatoid arthritis (RA), allergic asthma (AA), and systemic lupus erythematosus (SLE) [ 13 – 15 ]. In addition, elevated serum IL-38 levels at baseline can be used to predict virological response in telbivudine-treated patients with chronic hepatitis B [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Xue

Chen

et al. 2021

Virol J

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Background Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. Methods Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected. Results The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication. Conclusions Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.

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“…Nevertheless, specific datas were not shown. Furthermore, Xu et al (2020a) reported that compared with volunteers, the mRNA level of IL-38 in peripheral blood mononuclear cells (PBMCs) of SLE patients was increased. In vitro , silencing endogenous IL-38 in PBMCs caused an apparent augment in the lupus-associated mediators IL-6 and APRIL (a proliferation-inducing ligand) ( Fanouriakis et al, 2021 ).…”

Section: The Function Role Of Il-38 In Autoimmune Diseasesmentioning

confidence: 99%

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

et al. 2021

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Interleukin-38 (IL-38), a new cytokine of interleukin-1 family (IL-1F), is expressed in the human heart, kidney, skin, etc. Recently, new evidence indicated that IL-38 is involved in the process of different autoimmune diseases. Autoimmune diseases are a cluster of diseases accompanied with tissue damage caused by autoimmune reactions, including rheumatoid arthritis (RA), psoriasis, etc. This review summarized the links between IL-38 and autoimmune diseases, as well as the latest knowledge about the function and regulatory mechanism of IL-38 in autoimmune diseases. Especially, this review focused on the differentiation of immune cells and explore future prospects, such as the application of IL-38 in new technologies. Understanding the function of IL-38 is helpful to shed light on the progress of autoimmune diseases.

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IL‐38: A novel cytokine in systemic lupus erythematosus pathogenesis

Cited by 25 publications

References 39 publications

Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

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