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

• Published in: Seizure (London, England) Vol. 38; pp. 17 - 22
• Main Authors: Ni, Fen-Fen, Li, Cheng-Rong, Liao, Jian-Xiang, Wang, Guo-Bing, Lin, Su-Fang, Xia, Yu, Wen, Jia-Lun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2016
• Subjects: Child; Child, Preschool; Diet, Ketogenic - methods; Drug Resistant Epilepsy - blood; Drug Resistant Epilepsy - diet therapy; Female; Humans; Infant; Interleukin-17 - blood; Intractable epilepsy; Ketogenic diet; Male; Neurology; T-Lymphocytes, Regulatory; Th17 Cells; Treatment Outcome; Treg cells; Treg cells; Intractable epilepsy; Ketogenic diet; Th17 cells
• ISSN: 1059-1311; 1532-2688; 1532-2688
• DOI: 10.1016/j.seizure.2016.03.006

•Th17/Treg cell imbalance exists in intractable childhood epilepsy (IE).•Abnormal mTOR/HIF-1α signaling pathway affects Th17/Treg balance in IE.•Over-expression of HIF-1α may be due to abnormal expression of mTOR in IE.•KD can restore the mTOR/HIF-1α signaling pathway to a normal level in IE. The ketogenic diet (KD) 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. 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, HIF1α and Th17/Treg associated factors in purified CD4+CD25+ T and CD4+CD25− T cells. By one-way ANOVA, the proportion of circulating Th17 cells and expression of IL-17A and RORγt 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 KD (P<.05). In CD4+CD25+ T and CD4+CD25− T cells mTOR and HIF1α expression were significantly higher in IE patients (P<.05), however KD reduced mTOR and HIF1α 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). Our results suggest that Th17/Treg imbalance is characteristic of childhood IE, and may contribute to IE pathogenesis. KD treatment is able to correct this imbalance, probably via inhabiting the mTOR/HIF-1α signaling pathway.