Evaluation of the circulating levels of IL-33 in patients with osteoarthritis: role of rs1929992 variants

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-07-24 DOI:10.1016/j.cyto.2025.156996

Nahid Alimoradi , Fatemeh Jahankhah , Habibollah Jokardarzi , Mohammad Tahami , Negar Firouzabadi

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引用次数: 0

Abstract

Background

Osteoarthritis (OA) is among the common chronic health conditions which impacts many aspects of an individual’s life from physical function to mental health. Inflammation, in the joint as well as system inflammation is among the many mechanisms hypothesized to be involved in OA. IL-33 which belongs to the IL-1 family, is considered as an alarmin in OA. IL-33 binds to a group of receptors to stimulate signaling among which is the ST2L receptor that induced the activation of NFƙb, thus, working as a booster of the inflammatory cascade. Many polymorphisms have been identified on the IL-33 gene which are assumed to be associated with inflammatory diseases.

Methods

In the current double-blind placebo-controlled clinical trial study, patients diagnosed with knee OA were randomly divided into two groups: one group received metformin and the other received a placebo for 16 consecutive weeks (starting at 0.5 g/day, increasing to 1 g/day at week two, and increasing to 1.5 g/day for the remaining 14 weeks). Besides the evaluation of the clinical response to metformin using the Knee Injury and OA Outcome Score (KOOS) questionnaire, the serum levels of IL-33 was measured using enzyme-linked immunosorbent assay (ELISA) kits before (time 0) and after treatment (month 4). Genetic polymorphism of rs1929992 was assessed using in extracted DNAs using PCR-RFLP method.

Results

Serum levels of IL-33 were significantly higher in OA patients compered to healthy individuals (P<0.001). Mutant allele (G allele) of the rs1929992 was significantly associated with OA (P=0.028; OR=1.9; 95%CI: 1.02-3.6). AG+GG genotypes were also associated with OA (P=0.004; OR=3.8, 95%CI: 1.5-9.5). Metformin did not affect IL-33 levels (P>0.05). Variants of rs1929992 were not associated with response to metformin (P>0.05).

Conclusion

Our findings support the role of polymorphisms of IL-33 gene and circulating levels of IL-33 in OA. Drugs targeting IL-33 signaling pathway may propose beneficial effects in OA.

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评估骨关节炎患者循环IL-33水平：rs1929992变异的作用

骨关节炎（OA）是一种常见的慢性健康状况，它会影响个人生活的许多方面，从身体机能到心理健康。关节炎症和全身炎症是许多被认为与骨关节炎有关的机制之一。IL-33属于IL-1家族，被认为是OA的警示因子。IL-33结合一组受体刺激信号，其中ST2L受体诱导NFƙb的激活，从而作为炎症级联的助推器。在IL-33基因上发现了许多多态性，这些多态性被认为与炎症性疾病有关。方法在当前的双盲安慰剂对照临床试验研究中，诊断为膝关节OA的患者随机分为两组：一组服用二甲双胍，另一组服用安慰剂，连续16周（从0.5 g/天开始，第2周增加到1 g/天，其余14周增加到1.5 g/天）。除了使用膝关节损伤和OA结局评分（oos）问卷评估二甲双胍的临床反应外，还使用酶联免疫吸附试验（ELISA）试剂盒检测治疗前（第0时间）和治疗后（第4个月）血清IL-33水平。采用PCR-RFLP方法对提取的dna进行遗传多态性分析。结果OA患者血清IL-33水平明显高于健康人（P<0.001）。rs1929992突变等位基因（G等位基因）与OA显著相关(P=0.028；或= 1.9;95%置信区间:1.02—-3.6)。AG+GG基因型也与OA相关(P=0.004；Or =3.8, 95%ci: 1.5-9.5)。二甲双胍不影响IL-33水平（P>0.05）。rs1929992的变异与对二甲双胍的反应无关（P>0.05）。结论IL-33基因多态性与循环IL-33水平在OA发病中的作用。靶向IL-33信号通路的药物可能对OA有有益作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.