Unraveling the causal associations between systemic cytokines and six inflammatory skin diseases

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-01-01 DOI:10.1016/j.cyto.2024.156810

Waner Liu, Xu Zhang, Xiang Chen

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引用次数: 0

Abstract

Background

Previous observational studies have reported that systemic cytokines are associated with the risk of inflammatory skin diseases, but their conclusions remain controversial.

Method

We conducted a two-sample Mendelian randomization analysis to assess the relationship between systemic cytokines and six inflammatory skin disorders (including alopecia areata (AA), acne, atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis (PS) and vitiligo), based on datasets from EArly Genetics and Lifecourse Epidemiology (EAGLE) eczema consortium, acne GWAS conducted by Maris Teder Laving et al., IEU Open GWAS, and FinnGen database. Inverse-variance weighted (IVW) method was conducted in primary MR analysis, and supplemented by MR-Egger, weighted median, weighted mode, and MR-PRESSO.

Results

By integrating the findings from both primary and sensitivity analyses, we identified ten systemic cytokines linked to the risk of six skin diseases using the IVW method. Briefly, four cytokines increased the risk of corresponding skin diseases: β-nerve growth factor (β-NGF) to AA (p = 0.005) and HS (p = 0.001), interleukin-8 (p = 0.014) to acne; interleukin-5 (p = 0.042) to AD; interleukin-13 (p = 0.049) to PS. In the meantime, seven cytokines could have protective effect on specific skin diseases: interleukin-9 (p = 0.040) and interleukin-2 receptor subunit alpha (IL-2ra) (p = 0.020) on AA; macrophage inflammatory protein (MIP)-1β (p = 0.020) on acne; monokine induced by IFN-γ (p = 0.006) on AD; interleukin-16 (p = 0.038), MIP-1β (p = 0.017) and IL-2ra (p = 0.020) on PS.

Conclusions

This study reveals 13 causal associations between systemic cytokines and 6 skin diseases, offering new perspectives on the prevention and management of widespread inflammatory skin disorders.

查看原文本刊更多论文

揭示全身细胞因子与六种炎症性皮肤病之间的因果关系。

背景：先前的观察性研究报道了全身性细胞因子与炎症性皮肤病的风险相关，但其结论仍存在争议。方法：基于早期遗传学和生命过程流行病学（EAGLE）湿疹联盟、Maris Teder Laving等人开展的痤疮GWAS、IEU Open GWAS和FinnGen数据库的数据集，我们进行了两样本孟德尔随机化分析，以评估系统性细胞因子与六种炎症性皮肤病（包括斑秃（AA）、痤疮、特应性皮炎（AD）、化脓性皮炎（HS）、牛皮癣（PS）和白癜风）之间的关系。主要MR分析采用逆方差加权（IVW）方法，辅以MR- egger、加权中位数、加权模式和MR- presso。结果：通过整合原始分析和敏感性分析的结果，我们使用IVW方法确定了与六种皮肤病风险相关的10种全身细胞因子。简而言之，四种细胞因子增加相应皮肤病的风险：β-神经生长因子（β-NGF）增加AA （p = 0.005）和HS (p = 0.001)，白细胞介素-8 （p = 0.014）增加痤疮；白细胞介素-5对AD的影响（p = 0.042）；同时，白细胞介素-9 （p = 0.040）和白细胞介素-2受体亚单位α (IL-2ra) （p = 0.020）对特异性皮肤病具有保护作用；巨噬细胞炎症蛋白(MIP)-1β对痤疮的影响（p = 0.020）；IFN-γ诱导的AD单因子（p = 0.006）；白介素-16 (p = 0.038),MIP-1β （p = 0.017）和IL-2ra （p = 0.020）对ps的影响。结论：本研究揭示了全身细胞因子与6种皮肤病之间的13种因果关系，为广泛的炎症性皮肤病的预防和治疗提供了新的视角。

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.