Aerobic exercise is associated with divergent regulation of macrophage migration inhibitory factor and enhanced remyelination in experimental autoimmune neuritis.

The present study investigated the association between aerobic exercise preconditioning and macrophage migration inhibitory factor (MIF) expression, as well as myelination in the sciatic nerve in experimental autoimmune neuritis (EAN) rats. Female Lewis rats underwent 4-week swimming protocols including high-intensity daily, moderate-intensity daily, and moderate-intensity alternate-day (MOD-AltDay) regimens prior to EAN induction, with control groups of EAN without exercise and Sham operation. Assessment of disease severity, nerve conduction velocity, and sciatic nerve pathology revealed that the moderate-intensity alternate-day exercise regimen significantly delayed disease onset, lowered peak clinical scores, and improved neurological function. Molecular analyses demonstrated that this protective effect was mediated through divergent regulation of MIF: systemic MIF was substantially suppressed (27205.94 ± 4291.76 pg/ml versus EAN 71075.61 ± 10166.41 pg/ml; P <0.001) with concomitant reduction in macrophage infiltration, while local MIF expression within the sciatic nerve was significantly elevated (P <0.01), correlating with enhanced remyelination as evidenced by increased myelin sheath area (LFB: 67.42 ± 3.26% versus EAN 40.64 ± 9.63%, P <0.01) and elevated myelin basic protein expression (0.92 ± 0.14 AU versus EAN 0.59 ± 0.02 AU, P <0.05). Crucially, both high-intensity daily and moderate-intensity daily exercise protocols failed to confer comparable benefits. These findings indicate that the protective effect of MOD-AltDay exercise preconditioning on EAN is associated with tissue-specific regulation of MIF, and this change correlates with reduced systemic inflammation and enhanced local remyelination. Pharmacological/genetic studies are needed to confirm mechanisms and evaluate this exercise regimen as a non-pharmacological intervention for autoimmune neuropathy.