A Systematic Review & Meta-analysis: The Role of Cytokines in Adult Women 18 Years or Older with Fibromyalgia

Abstract

Background: Fibromyalgia (FM) is a chronic disease characterized by widespread pain of no confirmed etiology. Evidence supports an association between neuroinflammation and a FM diagnosis. The purpose of this study was to compare pro-inflammatory cytokines levels between having a diagnosis of FM in adult women 18 years or older and adult healthy females. Examining this difference may help identify an objective measure for FM diagnosis in adult females. Based on the law of pain theory, we hypothesize a dysregulation of inflammatory cytokines in FM adult females. Research methods: The 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines were followed. Six electronic databases, PubMed, CINAHAL, Cochrane, PsycINFO, Web of Science, and clinicaltrials.gov, were used to identify studies. The primarily studied variable is blood cytokines, including TNF-alpha, IL-1β, IL-6, IL-8. Non-interventional studies and interventional studies or secondary data analysis studies investigating blood cytokines and FM in adult females were included. Screening and data collection were done in multiple stages with two data abstractors and a third reviewer. Each study was appraised for quality using a scoring tool by Shiao and Yu (2016) and the risk for bias assessment tool by Cochrane was adapted for case-control studies. A meta-analysis was conducted to pool data and compare pro-inflammatory cytokines and adult FM females using the random-effects model. Result: Overall, the standardized mean difference (SMD) and confidence interval showed FM women had significantly higher blood cytokine levels for IL-6 and IL-8 compared to healthy controls (SMD = .34, CI = .08 to .60, p = .01). These results withstood multiple sensitivity analyses. In contrary to previous findings, being overweight was not a moderator of the association between blood cytokine levels and having FM in adult women. The quality of the included studies was moderate to high and evidence of publication bias was minimal. Four cytokines were studies in which IL-6 and IL-8 were the only two cytokines that maintained significance during the various sensitivity analyses. Conclusion: Findings from this study may be used as a basis for future research, explicitly investigating the incorporation of IL-6 and IL-8 in the diagnosis of FM in adult women. Keywords: fibromyalgia, fibrositis, fibromyositis, central nervous system centralization, cytokines, interleukins, tumor necrosis factor.