Does Inflammation Play a Role in Fatigue in Multiple Sclerosis?

Fatigue associated with multiple sclerosis (MS) affects up to 90% of individuals with the disease, impacting quality of life and causing disability. Because the symptom remains difficult to evaluate and treat, finding biomarkers of MS-related fatigue might aid clinicians in optimizing evaluation and treatment strategies.

In a new study published in the Journal of Inflammation Research, the authors sought to assess the role of MS-related central and peripheral inflammation and immunomediated endocrine dysregulation in the development of this symptom.

The researchers conducted an analysis of 27 studies that addressed the relationship between MS fatigue and inflammatory, immune, and endocrine factors. Among the selected studies involving central inflammatory and neuroendocrine processes, they found an inconsistency regarding the relationship between fatigue and orexin A system, the hypothalamus-pituitary-adrenal (HPA) axis, and cerebrospinal fluid inflammatory markers.

Although there were limited available data, serum proinflammatory cytokines seemed to be associated with MS fatigue, according to the findings. However, no link was found between MS fatigue and T-cell populations or other peripheral markers of inflammation.

Additionally, several trials showed differences in immune/inflammatory profiles between treated and naïve patients with MS, and downregulation of proinflammatory cytokines was observed among patients with MS administered disease-modifying therapies.

“Another issue to consider is the possible impact of MS treatments on fatigue per se,” the researchers noted in the study.

According to 1 cross-sectional study, higher fatigue rates were observed among patients with MS administered IFNb or glatiramer acetate compared with patients receiving natalizumab. In other studies, rituximab was found to induce fatigue in patients, natalizumab appeared to improve fatigue, and fingolimod did not seem to modify symptom severity. The study authors noted that more research is needed to understand the potential effects of MS therapies on fatigue perception and cytokine profiles.

Overall, the researchers concluded that future large-scale studies would benefit from comparing the relationship between fatigue and immune measures in patients with different disease phenotypes with and without disease-modifying drugs.

References

Chalah MA, Ayache SS. Is there a link between inflammation and fatigue in multiple sclerosis? Journal of Inflammation Research. 2018. https://doi.org/10.2147/JIR.S167199