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 cytokines levels in patients with diffuse CPS (fibromyalgia) versus healthy controls (HC).
Human studies published in English from the PubMed and 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).
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 to HC, while the chemokine eotaxin, was consistently raised in fibromyalgia . Meta-analysis showed significantly increased tumour necrosis factor alpha (TNF-α) (SMD=0.36, p = 0.0034, 95%CI=0.12-0.60; I2=71%, Q2 p = 0.0002), interleukin (IL)-6 (SMD=0.15, p = 0.045, %95CI=0.003-0.29; I2=39%, Q2 p = 0.059), IL- 8 (SMD=0.26, p = 0.01, 95%CI =0.05-0.47; I2=61%, Q2 p = 0.005) and IL-10 (SMD=0.61; %95 = 0.34-0.89, p < 0.001; I2 = 10%, Q2 p = 0.34) in fibromyalgia patients compared to HC.
We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared to HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8), and anti-inflammatory cytokines (IL-10) in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia.