越来越多的证据表明炎症细胞因子和粘连性囊膜炎 (AC) 之间存在联系。然而，导致 AC 的特定全身炎症细胞因子尚未明确。本研究采用孟德尔随机化 (MR) 来探索 41 种炎症细胞因子与 AC 之间的因果关系。在这项双向、两个样本的 MR 分析中，与 AC 相关的遗传变异源自全面的全基因组关联研究 (GWAS)。炎症细胞因子数据来自 GWAS 总结，涉及 8,293 名健康参与者。采用的主要 MR 方法是逆方差加权，辅以 MR-Egger、加权中位数、MR-多效性残差和和离群值进行敏感性分析。使用 Cochran's Q 检验评估异质性，并使用留一法验证 MR 结果。干扰素 γ 诱导蛋白 10 (IP-10) 水平升高（比值比 (OR) = 1.086，95% 置信区间(CI) = 1.002-1.178) 并调节激活、正常 T 细胞表达和分泌 (RANTES)（OR = 1.107，95% CI = 1.026-1.195）与 AC 风险增加相关。基质细胞衍生因子 1 α (SDF-1α)（OR = 0.879，95% CI = 0.793-0.974）和肿瘤坏死因子 α (TNF-α)（OR = 0.911，95% CI = 0.831）水平升高-0.999）与 AC 风险降低相关。此外，基因预测的 AC 与皮肤 T 细胞吸引 (CTACK) 水平升高（OR = 1.202，95% CI = 1.007-1.435）和白介素 17 (IL-17) 水平降低（OR = 0.678，95% CI = 1.007-1.435）相关（OR = 0.678，95% CI = 0.518-0.888）和白细胞介素-5 (IL-5)（OR = 0.786，95% CI = 0.654-0.944），通过逆方差加权 (IVW) 方法证实。本研究成功建立了遗传因素之间的因果关系。代理 IP-10、RANTES、SDF-1α 和 TNF-α 的循环水平以及 AC 风险。此外，AC 还有助于 CTACK 的增加以及 IL-17 和 IL-5 的减少。这一重大发现不仅增强了对 AC 发病机制的理解，而且为制定有效的临床管理策略带来了希望。版权所有 © 2024 Ouyang 和 Dai。

Mounting evidence suggests a connection between inflammatory cytokines and adhesive capsulitis (AC). However, the specific systemic inflammatory cytokines contributing to AC have not been clearly identified. This study employed Mendelian randomization (MR) to explore the causal relationships between 41 inflammatory cytokines and AC.In this bidirectional, two-sample MR analysis, genetic variations associated with AC were derived from a comprehensive genome-wide association study (GWAS). The inflammatory cytokines data were sourced from a GWAS summary involving 8,293 healthy participants. The primary MR method employed was inverse variance weighting, supplemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier for sensitivity analysis. Heterogeneity was assessed using Cochran's Q test, and the MR results were validated using the leave-one-out method.Elevated levels of interferon gamma-induced protein 10 (IP-10) (odds ratio (OR) = 1.086, 95% confidence interval (CI) = 1.002-1.178) and regulated on activation, normal T cell expressed and secreted (RANTES) (OR = 1.107, 95% CI = 1.026-1.195) were linked to an increased risk of AC. Increased levels of stromal cell-derived factor-1 alpha (SDF-1α) (OR = 0.879, 95% CI = 0.793-0.974) and tumor necrosis factor-alpha (TNF-α) (OR = 0.911, 95% CI = 0.831-0.999) were associated with a reduced AC risk. Moreover, genetically predicted AC exhibited associations with elevated cutaneous T cell attracting (CTACK) levels (OR = 1.202, 95% CI = 1.007-1.435) and diminished levels of interleukin-17 (IL-17) (OR = 0.678, 95% CI = 0.518-0.888) and interleukin-5 (IL-5) (OR = 0.786, 95% CI = 0.654-0.944), as confirmed through inverse-variance weighted (IVW) methods.The present study successfully establishes a causal association between genetically proxied circulating levels of IP-10, RANTES, SDF-1α, and TNF-α and the risk of AC. Additionally, AC contributes to an increase in CTACK and a decrease in IL-17 and IL-5. This significant finding not only enhances the understanding of the pathogenesis of AC but also holds promise for the development of effective clinical management strategies.Copyright © 2024 Ouyang and Dai.