Background/Purpose: Fibromyalgia is a chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, cognitive disturbances, and poor sleep. Despite accumulating evidence of immune involvement, a clear immunophenotype remains elusive. Previous studies have focused on a limited set of cytokines with inconclusive results. This study aims to explore a broader panel of proinflammatory, anti-inflammatory, and adaptive cytokines to identify immune abnormalities that may contribute to fibromyalgia pathology.

Methods: 46 patients diagnosed with fibromyalgia per the 2016 ACR criteria underwent peripheral blood sampling. Serum levels of 22 cytokines were analyzed at the University of Miami Immunology Lab and compared to age-matched normal controls using a percentile-based cutoff. Cytokines were categorized as pro-inflammatory (TNF-α, IL-6, IL-8, IL-1α, IL-1β, IFN-γ, IL-17), anti-inflammatory (IL-10, IL-4, IL-13), or adaptive (IL-12, IL-15, IL-23). Levels of soluble cytokine receptors (TNFR1 and TNFR2) were also measured. Levels were deemed abnormal if ≥50% of patients had values greater than the 90th percentile or less than the 10th percentile of the normal range. Flow cytometry was conducted in 25 patients to assess immune cell populations (CD8+, CD26+, CD11a+, CD56+, etc.).

Results: Fibromyalgia patients exhibited elevated levels of TNF-β, IL-5, IL-12, IL-15, IL-23, TNFR1, and TNFR2, suggesting heightened activation of both proinflammatory and adaptive pathways. IL-10, a key anti-inflammatory cytokine, was notably lower than average in most individuals. IL-1β, IL-6, and IL-17 levels exceeded the 90th percentile in a significant subset of patients, indicating innate immune activation. IL-8 elevations correlated with previously reported links to symptom duration. Flow cytometry revealed reduced frequencies of CD8+, CD26+, and CD11a+ cells, with values below normal in over half of the tested patients

Conclusion: Fibromyalgia patients demonstrate a coherent dysregulation in immune signaling, characterized by elevations in several proinflammatory and adaptive cytokines alongside suppression of anti-inflammatory mediators such as IL-10. These findings support hypotheses of central sensitization being partially driven by aberrant immune signaling, even in the absence of classical inflammation. IL-10 deficiency and elevated TNF/IL-23 axis components may represent mechanistic targets for therapeutic intervention. Further research is needed to validate these biomarkers and explore causal mechanisms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/broad-cytokine-dysregulation-in-fibromyalgia-patients-a-pilot-immune-profiling-study/