IL-38: A New Player in Inflammatory Autoimmune Disorders

Xie, Lihui; Huang, Zhaofeng; He, Ling; Liu, Xiuxing; Zheng, Song Guo; Su, Wenru

doi:10.3390/biom9080345

Cited by 75 publications

(68 citation statements)

References 128 publications

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“…IL-38 is expressed in several tissues but mainly in skin and proliferating B cells of the tonsils (Dinarello 2018). IL-38 exists intracellularly as a precursor full-length form called IL-38 (aa1-152) and must be cleaved at the N-terminus before it is secreted extracellularly as an active form (Xie et al 2019). Unlike other members of the IL-1 family, IL-38 is not processed by caspase 1, but neither the processing enzyme nor the active form are presently known (Xie et al 2019).…”

Section: Il-38mentioning

confidence: 99%

“…IL-38 exists intracellularly as a precursor full-length form called IL-38 (aa1-152) and must be cleaved at the N-terminus before it is secreted extracellularly as an active form (Xie et al 2019). Unlike other members of the IL-1 family, IL-38 is not processed by caspase 1, but neither the processing enzyme nor the active form are presently known (Xie et al 2019). The main cellular targets of IL-38 and its receptors remain obscure.…”

Section: Il-38mentioning

confidence: 99%

“…The main cellular targets of IL-38 and its receptors remain obscure. The main receptor IL-36R, the cofactor IL1-R9, and IL-1 receptor accessory protein-like 1 (IL-1RAPL1) seem to be involved in the inhibitory action of IL-38 (Xie et al 2019). IL-38 binds to IL-1R6 that results in the recruitment of IL-1R9, the formation of a trimeric signaling complex, and the triggering of downstream anti-inflammatory signaling pathways (van de Veerdonk et al 2012).…”

Section: Il-38mentioning

confidence: 99%

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IL-1 Superfamily Members and Periodontal Diseases

et al. 2020

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Periodontitis is a complex, multifactorial chronic disease involving continuous interactions among bacteria, host immune/inflammatory responses, and modifying genetic and environmental factors. More than any other cytokine family, the interleukin (IL)–1 family includes key signaling molecules that trigger and perpetuate periodontal inflammation. Over the years, the IL-1 family expanded to include 11 members of cytokines, some with agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ), receptor antagonists (IL-1Ra, IL-36Ra), and 2 anti-inflammatory cytokines (IL-37, IL-38). The IL-1 receptor antagonist (IL-1Ra) has emerged as a pivotal player in the defense against periodontitis. IL-33 primarily induces the production of Th2-associated cytokines but acts as an “alarmin” via stimulation of mast cells. The IL-36 subclass of cytokines may be important in regulating mucosal inflammation and homeostasis. IL-37 suppresses innate and acquired immune responses. IL-38 is the most recent member of the IL-1 superfamily and has anti-inflammatory properties similar to those of IL-37 but through different receptors. However, limited evidence exists regarding the role of IL-37 and IL-38 in periodontitis. Despite the development of IL-1 blocking agents, therapeutic blockade of select IL-1 family members for periodontitis has only been partially investigated in preclinical and clinical research, while the development of IL-37 and IL-38 as novel anti-inflammatory drugs has not been considered adequately. Here, we review the key properties of the IL-1 family members and provide insights into targeting or promoting select cytokines as new therapeutic agents.

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Section: Il-38mentioning

confidence: 99%

Section: Il-38mentioning

confidence: 99%

Section: Il-38mentioning

confidence: 99%

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IL-1 Superfamily Members and Periodontal Diseases

et al. 2020

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“…The newest member of this family, IL-38, previously named IL-1HY2, has been suggested to function in an anti-inflammatory manner. This viewpoint originates from the reported sequential homology of this cytokine with IL-36Ra and IL-1Ra, two other members of the IL-1 cytokine family with proven anti-inflammatory properties [2]. Growing evidence has illustrated the role of IL-38 in the pathological pathways of several diseases; polymorphisms of the gene encoding this cytokine have been shown to be associated with ankylosing spondylitis [3], psoriatic arthritis [4], and rheumatoid arthritis [5].…”

Section: Introductionmentioning

confidence: 99%

Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients

et al. 2020

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Objective: Interleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc). Subjects and Methods: A total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA. Results: Levels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls. Conclusion: The higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.

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“…IBD patients seem to have abnormal expression of this interleukin, contributing to the inflammatory process. This scenario is associated with abdominal pain, bleeding, gas production, diarrhea, decrease quality of life, and leads to significant morbidity [33,34,35].…”

Section: Discussionmentioning

confidence: 99%

Omega Fatty Acids and Inflammatory Bowel Diseases: An Overview

Marton

Goulart

Carvalho

et al. 2019

IJMS

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Inflammatory bowel diseases (IBD) are chronic, inflammatory processes that affect the gastrointestinal tract and are mainly represented by ulcerative colitis (UC) and Crohn’s disease (CD). Omega 3 (ω3) fatty acids (eicosapentanoic acid and docosahexaenoic acid) show an indispensable role in the inflammatory processes and, for these reasons, we aimed to review the effects of these acids on UC and CD. Databases such as PUMED and EMBASE were searched, and the final selection included fifteen studies that fulfilled the inclusion criteria. The results showed that ω3 fatty acids reduce intestinal inflammation, induce and maintain clinical remission in UC patients, and are related with the reduction of proinflammatory cytokines, decrease disease activity and increase the quality of life of CD patients. Furthermore, the consumption of these fatty acids may be related to a reduced risk of developing IBD. Many studies have shown the beneficial effects of ω3 as adjunctive in the treatment or prevention of UC or CD. Nevertheless, most were performed with a small number of patients and there are many variations in the mode of consumption, the type of food or the type of formulation used. All these factors substantially interfere with the results and do not allow reliable comparisons.

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IL-38: A New Player in Inflammatory Autoimmune Disorders

Cited by 75 publications

References 128 publications

IL-1 Superfamily Members and Periodontal Diseases

IL-1 Superfamily Members and Periodontal Diseases

Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients

Omega Fatty Acids and Inflammatory Bowel Diseases: An Overview

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