Alpha-Tocopherol Ameliorates Experimental Autoimmune Neuritis by Exerting Antioxidant Effects and Suppressing Cytokine Production

Introduction: Guillain-Barré syndrome (GBS) is an autoimmune neuropathy mediated by insult of anti-ganglioside antibodies and subsequent complement activation. Oxidative toxicity, resulting from insufficiently maintained cellular redox levels, has also been contributed to GBS pathogenesis; however, antioxidant therapy for GBS patients has not yet been established. The effectiveness of α-tocopherol (αT), a natural antioxidant, was evaluated as a treatment for experimental autoimmune neuritis (EAN), using an animal model of human GBS. Methods: Female Lewis rats, immunized with 125 μg of synthetic peptide from bovine P2 protein, were injected with 100 mg/kg of intraperitoneal αT on only day 6 or on both days 6 and 13 post-immunization (p.i.). Lipid peroxidation products, histological alterations, and cytokine expression in the cauda equina and/or popliteal lymph nodes were sequentially evaluated. Results: Flaccid paralysis developed from the tail tip at days 11-13 p.i. in both αT-treated rats and non-treated control rats. The latter gradually progressed to flaccid paraplegia, and reached a peak of motor impairment on day 16 p.i., followed by spontaneous recovery. Double αT administration, but not single administration, significantly improved the clinical course of EAN, decreased the level of the lipid peroxidic marker N epsilon-(hexanoyl) lysine, and suppressed mRNA expression of interferon-gamma and interleukin-10 in the popliteal lymph nodes and cauda equina. Histologically, αT treatment showed reduced demyelination in the cauda equina compared to control rats. Conclusions: Alpha-T ameliorated EAN by suppressing the production of pro-inflammatory cytokines and preventing oxidative damage. This demonstrates the potential of natural antioxidant treatment for GBS.