Inflammatory proteins are altered in chronic fatigue syndrome – a systematic review and meta-analysis, by Rebecca Strawbridge, Maria-Laura Sartor, Fraser Scott, Anthony J Cleare in Neuroscience & Biobehavioral Reviews, August 26, 2019 []



  • 42 studies meta-analysed, testing 20 proteins between patients with CFS and controls
  • Patients had higher levels of 5 cytokines than controls (TNF, IL-2, IL-4, TGFb, CRP)
  • Group differences were not significant for 12 proteins
  • Results are heterogeneous but provide some support for an inflammatory role in CFS

Review abstract:

Immune dysfunction has been posited as a key element in the aetiology of chronic fatigue syndrome (CFS) since the illness was first conceived.  However, systematic reviews have yet to quantitatively synthesise inflammatory biomarkers across the literature.

We undertook a systematic review and meta-analysis to quantify available data on circulating inflammatory proteins, examining studies recruiting patients with a CFS diagnosis and a non-affected control group.

Results were meta-analysed from 42 studies. Patients with CFS had significantly elevated tumour necrosis factor (ES = 0.274, p < 0.001), interleukin-2 (ES = 0.203, p = 0.006), interleukin-4 (ES = 0.373, p = 0.004), transforming growth factor-β (ES = 0.967, p < 0.001) and c-reactive protein (ES = 0.622, p = 0.019). 12 proteins did not differ between groups.

These data provide some support for an inflammatory component in CFS, although inconsistency of results indicates that inflammation is unlikely to be a primary feature in all those suffering from this disorder. It is hoped that further work will elucidate whether there are subgroups of patients with clinically-relevant inflammatory dysfunction, and whether inflammatory cytokines may provide a prognostic biomarker or moderate treatment effects.

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