The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy

Purpose: The ketogenic diet (MD) is an effective treatment for intractable epilepsy (IE), however the therapeutic mechanism is still unclear. This study was designed to investigate T helper type 17/regulatory T cell (Th17/Treg) levels in children with IE and age-matched healthy controls following KD. Method: Circulating levels of Th17/Treg cells were analyzed by flow cytometry. Plasma concentration of interleukin (IL)-17 was measured by cytometric bead array assay. Real-time PCR was performed to measure mRNA levels of mTOR, HIF1 alpha and Th17/Treg associated factors in purified CD4(+)CD25(+) T and CD4(+)CD25(-) T cells. Results: By one-way ANOVA, the proportion of circulating Th17 cells and expression of IL-17A and ROR gamma t were significantly higher (P < .05), while the proportion of circulating Tregs and expression of Foxp3, GITR, CTLA-4 were significantly lower (P < .05) in IE patients than healthy subjects. However, these alternations were reversed following MD (P < .05). In CD4(+)CD25(+) T and CD4(+)CD25(-) T cells mTOR and HIF1 alpha expression were significantly higher in IE patients (P < .05), however KD reduced mTOR and HIF1 alpha expression (P < .05). The plasma IL-17A concentrations were higher in IE patients than controls (P < .05). KD partially reduced IL-17A levels (P < .05). Conclusion: Our results suggest that Th17/Treg imbalance is characteristic of childhood 1E, and may contribute to IE pathogenesis. KD treatment is able to correct this imbalance, probably via inhabiting the mTOR/HIF-1 alpha signaling pathway. (C) 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.