Temporal relationship between neurofilament light chain and cytokines involved in T helper-17 lymphocyte signaling in the blood of experimental autoimmune encephalomyelitis mice

Background

Multiple sclerosis (MS) is an autoimmune neuroinflammatory disease leading to eventual neurodegeneration. There is a strong interest in using blood biomarkers to detect the disease onset and monitor disease progression in MS. One such biomarker is neurofilament light chain (NfL) that reflects axonal damage or neurodegeneration. Proinflammatory cytokines involved in T-helper 17 (Th17) lymphocyte signaling are potential blood biomarkers of neuroinflammation.

Methods

We induced experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, in female C57BL/6 mice and measured the progression of EAE using a clinical score. We collected blood from EAE mice on the post-immunization days 7, 10, 16, or 22 and measured NfL concentrations using single molecule array (SIMOA) technology. We also measured concentrations of cytokines related to Th17 using xMAP immune assay technology (Luminex) from the same mice.

Results

We found that the concentration of NfL began to rise at the onset of clinical symptoms on the post-immunization day 10 and peaked on day 16, closely correlating with the clinical score. However, the concentrations of several proinflammatory cytokines, including IFN-γ, IL-6, IL-17A, IL-22, and TNF-α, were already elevated even before the onset of the clinical symptoms and did not correlate positively with the clinical scores.

Conclusion

Our results confirmed the utility of NfL as a blood biomarker for disease progression in MS. The elevation of multiple proinflammatory cytokines concentrations in the blood of the same EAE mice in the presymptomatic stage suggested that blood biomarkers for neuroinflammation increased before blood biomarkers for neurodegeneration during the disease course in EAE.