Inflamed brains and dementia often share a surprising link: inflammation can ripple out to the muscles, sparking rapid fatigue even after the brain has begun to calm down. A new study advances this idea by identifying a protein that travels from the inflamed brain into the bloodstream and then into muscles, where it disrupts how these muscles generate energy. The researchers shared their findings in Science Immunology, highlighting a chain of events that could help explain why some infections and neurodegenerative conditions leave people with lingering weakness.
In carefully controlled experiments, scientists recreated three disease scenarios in model organisms: bacterial infection with Escherichia coli, SARS-CoV-2 infection, and an Alzheimer’s-like condition. They observed that the inflammatory proteins characteristic of these diseases produced brain damage through reactive oxygen species. At the same time, brain cells released interleukin-6 (IL-6) into the bloodstream. Once IL-6 reached muscles, it dampened the cells’ energy production, making muscle activity less efficient and more tiring. This dual impact—from brain to muscle—helps explain how cognitive inflammation can translate into physical fatigue and reduced daily function.
The behavioral consequence in the animals was a measurable drop in motor activity, which persisted long after the animals had recovered from the initial insults. Importantly, the work aligns with a growing body of clinical observations in humans, where patients with bacterial meningitis, dementia, or coronavirus have shown signs of muscle weakness and fatigue during and after illness. Some of these effects appear to reflect the same IL-6–driven energy shortfall in muscle tissue, suggesting a common inflammatory pathway that crosses organ systems.
Beyond the animal studies, the research also touches on potential therapeutic angles. Inflammation in the brain is a recognized target for a range of conditions, and JAK inhibitors—drugs already used to treat arthritis and several inflammatory disorders—have demonstrated the ability to reduce brain inflammation in various settings. While the study does not imply a universal cure, it points to the possibility that reducing inflammation or blocking IL-6 signaling could help preserve muscle energy and function when the brain is under inflammatory siege.
Looking ahead, scientists are interested in confirming whether the Exact brain-to-muscle signaling pathway observed in model systems behaves the same way in people. If the same protein and IL-6 mechanism are at work in humans, clinicians could develop strategies to protect muscle energy reserves during bouts of brain inflammation, potentially improving recovery times and overall quality of life for patients in North America and around the world. Ongoing research in clinical populations, including those with meningitis, dementia, and viral infections, is expected to shed light on how these discoveries translate to patient care and rehabilitation.
Collectively, the findings contribute to a broader understanding of how brain inflammation can influence bodily function. They underscore the idea that mental and physical health are tightly intertwined, and they highlight a path toward interventions that might mitigate fatigue and weakness by interrupting inflammatory signals before they compromise muscle energy production. The work in Science Immunology thus adds an important piece to the puzzle of how inflammatory diseases affect the body beyond the brain, offering a hopeful direction for future treatment strategies that can help patients maintain strength and activity during and after inflammatory illnesses. (Cited from Science Immunology, with corroborating observations in clinical studies of meningitis, dementia, and COVID-19 patients.)