Is fibromyalgia associated with a unique cytokine profile?

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 cytokines levels in patients with diffuse CPS (fibromyalgia) versus healthy controls (HC). Methods: 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). 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 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. Conclusion: 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