Inflammatory proteins are altered in chronic fatigue syndrome-A systematic review and meta-analysis.
Strawbridge, Rebecca, Sartor, Maria-Laura, Scott, Fraser et al. · Neuroscience and biobehavioral reviews · 2019 · DOI
Quick Summary
This research review looked at 42 studies measuring inflammatory proteins (substances in the blood linked to inflammation) in people with ME/CFS compared to healthy people. The researchers found that people with ME/CFS had higher levels of five specific inflammatory proteins, but twelve other proteins were similar to healthy controls. This suggests that inflammation may play a role in ME/CFS for some patients, but it's likely not the main problem for everyone with the condition.
Why It Matters
This is the first quantitative synthesis of inflammatory biomarkers across ME/CFS literature, providing objective evidence that immune dysfunction occurs in this disease. Understanding which inflammatory proteins are consistently elevated could help identify ME/CFS subgroups and guide future targeted treatment development.
Observed Findings
Tumour necrosis factor (TNF) was significantly elevated in ME/CFS patients (p<0.001)
Interleukin-4 (IL-4) showed the largest effect size among significant findings (ES=0.373, p=0.004)
Transforming growth factor-β (TGF-β) was substantially elevated (ES=0.967, p<0.001), the largest effect observed
C-reactive protein (CRP) was significantly elevated (p=0.019)
Twelve inflammatory proteins examined did not differ significantly between ME/CFS patients and controls
Inferred Conclusions
Immune dysfunction involving specific inflammatory proteins is present in ME/CFS, supporting an inflammatory component in disease pathogenesis
Inflammation is unlikely to be a universal primary feature across all ME/CFS patients, given heterogeneous results
ME/CFS may comprise inflammatory and non-inflammatory subgroups that require different diagnostic and therapeutic approaches
Inflammatory cytokines warrant investigation as potential prognostic biomarkers or predictors of treatment response in specific patient subsets
Remaining Questions
Which ME/CFS patients have clinically relevant inflammatory dysfunction, and can they be identified by specific inflammatory profiles?
What This Study Does Not Prove
This study does not establish that inflammation causes ME/CFS or is the primary driver of the disease in all patients. Elevated inflammatory proteins may be a consequence of other underlying dysfunction rather than a cause, and the variation across studies suggests biological heterogeneity that prevents one-size-fits-all conclusions about inflammation's role.
Are elevated inflammatory proteins causally related to ME/CFS symptoms, or are they secondary consequences of other biological abnormalities?
Do different inflammatory patterns predict different disease trajectories, treatment responses, or clinical outcomes?
What explains the substantial heterogeneity between studies—methodological differences, patient population characteristics, or true biological variation?