Introduction: Multiple Sclerosis (MS) is a chronic autoimmune disorder marked by neuroinflammation, demyelination, and neurodegeneration. Zinc is crucial for immune regulation, but its impact on inflammatory cytokines in MS is not well understood. This study examined how dietary zinc status influences pro-inflammatory cytokine release in spinal cord tissue using a cuprizone-induced rat model of MS.
Methods: The experimental cohort comprised 46 adult male Wistar rats, randomly allocated into five groups: Control (n=6) and four experimental groups “G” (n=10 each). G1 served as the untreated Control. G2, Sham-MS received daily oral gavage of carboxymethyl cellulose (CMC) solution-used as the vehicle for cuprizone-administered at 1% of their daily feed intake for 8 weeks. G3, G4, and G5 underwent MS induction via daily gavage of cuprizone dissolved in CMC at 1% of daily feed intake over the same period. G4 was maintained on a zinc-deficient diet (50 µg/kg zinc), whereas G5 received intraperitoneal zinc sulfate supplementation at 5 mg/kg/day. Disease progression was assessed by Rotarod performance and Myelin Basic Protein gene expression. Spinal cord levels of TNF-α, IL-1β, and IL-6 were measured by ELISA.
Results: Multiple sclerosis induction significantly increased TNF-α, IL-1β, and IL-6 levels (p <0.05), especially in zinc-deficient rats. Zinc supplementation attenuated these cytokine elevations, normalizing them to control levels (p <0.05). Functional and molecular data confirmed reduced disease severity with zinc repletion.
Conclusion: Our findings reveal that zinc status is a critical modulator of neuroinflammation in an experimental MS model. Inflammatory cytokine levels in the spinal cord were significantly higher in both MS and zinc-deficient MS groups, confirming local inflammation associated with demyelination. Furthermore, zinc supplementation demonstrated a regulatory effect by suppressing the increase in inflammatory cytokines in the experimental MS model. These results may point to the therapeutic potential of zinc in MS management.
Keywords: IL-1β, IL-6, multiple sclerosis, neuroinflammation, TNF-α, zinc