Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation?
Sun, Yuanjie, Koyama, Yoshihisa, Shimada, Shoichi · Frontiers in aging neuroscience · 2022 · DOI
Quick Summary
This review explores how inflammation in the body's organs—like the gut, lungs, or joints—can trigger inflammation in the brain. The authors describe several pathways by which this happens, including damage to the protective barrier around the brain, activation of immune cells in the brain, and communication through nerves connecting organs to the brain. ME/CFS is highlighted as one disease where this peripheral-to-brain inflammation mechanism may be important.
Why It Matters
ME/CFS is explicitly identified as a condition where peripheral inflammation may drive brain inflammation, a potential mechanism underlying symptoms like cognitive dysfunction and neurological complications. Understanding these pathways could lead to therapeutic targets aimed at interrupting the communication between peripheral inflammation and the brain. This framework helps explain why treating only peripheral symptoms may be insufficient if neuroinflammation is a primary driver of ME/CFS.
Observed Findings
Multiple pathways can transmit peripheral organ inflammation to the brain, including blood-brain barrier disruption, activation of glial cells (microglia and astrocytes) via systemic immune signals, and signaling through autonomic nerves via the organ-brain axis
ME/CFS is grouped among diseases capable of triggering neuroinflammation through peripheral organ inflammation mechanisms
Different brain regions show variable susceptibility to inflammatory signals depending on the pathway of transmission
Inferred Conclusions
Systemic inflammation from peripheral organs can cause neuroinflammation through multiple interconnected mechanisms rather than a single pathway
ME/CFS may involve peripheral-to-central inflammation signaling, suggesting that understanding these mechanisms could improve treatment strategies
The blood-brain barrier, glial cells, and autonomic signaling are key targets where peripheral inflammation might be interrupted before affecting the brain
Remaining Questions
Which of these three pathways (BBB disruption, glial activation, autonomic signaling) predominates in ME/CFS patients, and do individual patients vary?
What specific peripheral organs or inflammatory markers in ME/CFS most reliably predict neuroinflammation?
Can interventions that target these pathways (e.g., BBB stabilization, glial modulation, autonomic support) reduce both peripheral and brain inflammation in ME/CFS?
What This Study Does Not Prove
This review does not provide empirical evidence that peripheral inflammation actually causes neuroinflammation in ME/CFS patients specifically—it describes plausible mechanisms identified in other diseases. The study does not establish which of these pathways (BBB disruption, glial activation, or autonomic signaling) is most important in ME/CFS. It cannot prove causation, only propose mechanistic frameworks based on existing literature.