Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

Esmaeilzadeh, Abdolreza; Bahmaie, Nazila; Nouri, Elham; Hajkazemi, Mohammad Javad; Rafie, Maryam Zareh

doi:10.3390/ijms222212552

Cited by 9 publications

(8 citation statements)

References 195 publications

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“…IL-38 is thought to be an ancestral gene intended to counteract the pro-inflammatory effects of IL-1 (136). In humans, IL-38 is found in several organs such as the tonsils, skin, fetal liver, heart, and placenta, but in future studies it will certainly be found in many other organs (137). The anti-inflammatory effect of IL-38 is homologous with two anti-receptors, IL-36Ra (about 40%) and IL-1Ra (about 40%), sharing the anti-inflammatory effect (138).…”

Section: Il-38 Dumping Il-1 Induced Inflammationmentioning

confidence: 96%

Activation of Mast Cells by Neuropeptides: The Role of Pro-inflammatory and Anti-Inflammatory Cytokines

Lauritano¹,

Mastrangelo²,

D’Ovidio³

et al. 2023

Preprint

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Mass cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in scientific literature and is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptides and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

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Section: Il-38 Dumping Il-1 Induced Inflammationmentioning

confidence: 96%

Activation of Mast Cells by Neuropeptides: The Role of Pro-inflammatory and Anti-Inflammatory Cytokines

Lauritano¹,

Mastrangelo²,

D’Ovidio³

et al. 2023

Preprint

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“…The study concluded that IL‐38 may exert a protective role against immune system hyperactivity, and may alleviate induced lung inflammation 11 . Besides, it has been indicated that dysregulated serum levels of IL‐38 are linked to immunopathogenesis of several inflammatory and immune‐mediated disorders, as well as lung‐related diseases 12 …”

Section: Introductionmentioning

confidence: 99%

“… 11 Besides, it has been indicated that dysregulated serum levels of IL‐38 are linked to immunopathogenesis of several inflammatory and immune‐mediated disorders, as well as lung‐related diseases. 12 …”

Section: Introductionmentioning

confidence: 99%

“…11 Besides, it has been indicated that dysregulated serum levels of IL-38 are linked to immunopathogenesis of several inflammatory and immune-mediated disorders, as well as lungrelated diseases. 12 Due to limited data on IL-38 and COVID-19, the current study examined serum levels of IL-38 in patients with COVID-19 and healthy controls to evaluate the potential role of this cytokine in pathogenesis of COVID-19 infection. Further, disease severity (moderate, severe, and critical), as well as patient-related parameters (age, gender, body mass index and chronic disease status) were taken into account in the evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of interleukin‐38 levels in serum of patients with coronavirus disease 2019

Al-bassam

Al-Karaawi

Sharquie

et al. 2022

Journal of Medical Virology

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Interleukin‐38 (IL‐38) has recently been considered as a cytokine with anti‐inflammatory properties in viral respiratory infections, particularly coronavirus disease 19 (COVID‐19), but the evidence has not been well elucidated. Therefore, a case‐control study was conducted to determine IL‐38 serum levels in 148 patients with COVID‐19 (45 moderate, 55 severe, and 48 critical) and 113 controls. Results demonstrated that IL‐38 levels did not show significant differences between patients and controls (68.7 [interquartile range: 62.7–75.6] vs. 67.7 [58.0–82.6] pg/ml; probability = 0.457). Similarly, patients stratified by disease severity, age group, gender, or chronic disease showed no significant differences between IL‐38 levels in each stratum. Whereas, overweight/obese patients had a significantly lower median of IL‐38 compared to normal‐weight patients. Further, IL‐38 showed significantly higher levels in the age group ≥50 years of patients with critical illness than in the age group <50 years. Female patients with severe disease also showed significantly elevated levels of IL‐38 compared to male patients. In conclusion, the study indicated that serum IL‐38 levels were not affected by COVID‐19 infection, but the distribution of patients according to disease severity, age, gender, and body mass index may better reveal the role of IL‐38 in disease pathogenesis.

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“…Interleukin‐38 (IL‐38) is a member of the IL‐1 family, which binds to IL‐36 receptor (IL1RL2) as an antagonist to exert an anti‐inflammation effect (Esmaeilzadeh et al, 2021 ; Lai et al, 2022 ; van de Veerdonk et al, 2012 ). Also, IL1RL2 was reported as a candidate gene‐related soluble ST2 those elevated levels reflected the degree of vascular injury (Jiang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner

Kurose

Matsubara

Yoshino

et al. 2023

Physiological Reports

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Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. is a member of the IL-1 family, which binds to IL-36 receptor (IL1RL2) and has an anti-inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL-38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II-induced AAA model with or without IL-38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor-α and treated with or without IL-38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL-38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2 + macrophage accumulation along with matrix metalloproteinase (MMP)-2 and -9 expression was observed in mouse AAA. IL-38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP-2 and -9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP-2, and MMP-9 production and spindle-shaped changes were significantly suppressed by IL-38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL-38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL-38 depend on the p38 pathway. IL-38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL-38 may be a novel therapy for AAA patients.

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Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

Cited by 9 publications

References 195 publications

Activation of Mast Cells by Neuropeptides: The Role of Pro-inflammatory and Anti-Inflammatory Cytokines

Activation of Mast Cells by Neuropeptides: The Role of Pro-inflammatory and Anti-Inflammatory Cytokines

Evaluation of interleukin‐38 levels in serum of patients with coronavirus disease 2019

Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner

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