Vollmer-Conna, U, Lloyd, A, Hickie, I et al. · The Australian and New Zealand journal of psychiatry · 1998 · DOI
This review examines whether immune system problems might cause ME/CFS symptoms, particularly in the brain. The researchers found that while immune chemicals called cytokines are likely involved in ME/CFS, the results from studies measuring these chemicals in the blood have been mixed and unclear. They suggest that abnormal cytokine activity happening directly inside the brain—rather than in the bloodstream—may be more important for explaining the neurological symptoms patients experience.
This work provides a framework for understanding how immune dysfunction translates into ME/CFS brain symptoms, shifting focus from blood-based immune markers to central nervous system processes. This perspective has influenced subsequent research into neuroinflammation and glial dysfunction in ME/CFS, making it foundational for modern pathophysiological investigations.
This review does not definitively prove that cytokines cause ME/CFS or establish causation—it examines associations and proposes mechanisms. It does not provide direct evidence of CNS cytokine abnormalities, as cerebrospinal fluid and brain tissue studies were limited at the time. The inconclusive peripheral cytokine findings mean this review cannot confirm abnormal circulating immune markers as a primary biomarker.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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