纤维肌痛是否与独特的细胞因子谱相关？系统评价和荟萃分析。
Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis.
机构信息
University College London Medical School, London, UK.
Centre for Inflammation and Tissue Repair, London, UK.
出版信息
Rheumatology (Oxford). 2021 Jun 18;60(6):2602-2614. doi: 10.1093/rheumatology/keab146.
OBJECTIVES
The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokine levels in patients with diffuse CPS (fibromyalgia) vs healthy controls (HC).
METHODS
Human studies published in English from the PubMed, MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO (CRD42020193774).
RESULTS
Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared with HC, while the chemokine eotaxin, was consistently raised in fibromyalgia. Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P = 0.0034; I2 = 71%, Q2P = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P = 0.045; I2 = 39%, Q2P = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P = 0.01; I2 = 61%, Q2P = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P < 0.001; I2 = 10%, Q2P = 0.34) in fibromyalgia patients compared with HC.
CONCLUSION
We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared with HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia.
目的
原发性慢性疼痛综合征（CPS）的病因仍存在争议。本研究旨在系统评估弥漫性 CPS（纤维肌痛）患者与健康对照组（HC）之间循环细胞因子水平的差异。
方法
系统检索 PubMed、MEDLINE/Scopus 和 Cochrane 数据库中自成立以来至 2020 年 1 月发表的英文人类研究。纳入了具有基线细胞因子测量值的全文横断面或纵向研究，报告了纤维肌痛患者与 HC 之间循环细胞因子水平的差异。使用随机效应荟萃分析模型报告汇总效应和 95%置信区间。本研究已在 PROSPERO（CRD42020193774）注册。
结果
最初的搜索得到了 324 篇论文，确定了 29 项研究（2458 名参与者）符合系统评价的纳入标准，22 项研究（1772 名参与者）适合荟萃分析。系统分析显示了支持纤维肌痛患者与 HC 相比具有不同细胞因子水平趋势的可重复发现，而趋化因子 eotaxin 在纤维肌痛中始终升高。荟萃分析显示 TNF-α[标准化均数差（SMD）=0.36，95%CI：0.12，0.60，P=0.0034；I2=71%，Q2P=0.0002]、IL-6（SMD=0.15，95%CI：0.003，0.29，P=0.045；I2=39%，Q2P=0.059）、IL-8（SMD=0.26，95%CI：0.05，0.47，P=0.01；I2=61%，Q2P=0.005）和 IL-10（SMD=0.61，95%CI：0.34，0.89，P<0.001；I2=10%，Q2P=0.34）在纤维肌痛患者中均显著高于 HC。
结论
我们发现纤维肌痛患者与 HC 相比，外周血细胞因子谱存在显著差异。然而，荟萃分析中，与纤维肌痛相关的特征性特征包括促炎细胞因子（TNF-α、IL-6、IL-8）和抗炎细胞因子（IL-10），以及趋化因子（eotaxin）特征。需要进一步的研究来阐明细胞因子在纤维肌痛中的作用。
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