Effects of ketogenic diet on helper T cells in patients with intractable epilepsy / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the effects of ketogenic diet ( KD) treatment on helper T cell subsets in children with intractable epilepsy( IP) . Methods Thirty-five children with IP and eighteen age-matched healthy subjects were enrolled in this study.The percentages of CD3+CD8-IFN-γ+( Th1 ) cells, CD3+CD8-IL-17A+(Th17) cells and CD4+CD25+Foxp3+(Treg) cells were analyzed by flow cytometry.Re-al-time PCR assay was performed to evaluate the expression of T-bet, ROR-γ, IFN-γ, IL-17A and peroxi-some proliferator activated receptorγ( PPAR-γ) at mRNA level in CD4+CD25-T cells and the transcription-al levels of Foxp3, GITR, CTLA-4 and PPAR-γin CD4+CD25+T cells.The concentrations of cyclooxygen-ases-2 (COX-2) and prostaglandin F2a (PGF2α) in plasma samples were measured by enzyme-linked im-munosorbent assay.The expression of IL-17A and IFN-γin plasma samples were detected by using cytomet-ricbeadarray(CBA).Results (1)ThepercentagesofTregcellsinperipheralbloodsamplesfrompa-tients with IP were lower than those in healthy subjects (P<0.05), which were significantly increased with the treatment of KD (P<0.05).The percentages of Th17 and Th1 cells in patients with IP were significantly higher than those in healthy children (P<0.05), but were remarkably decreased with the treatment of KD (P<0.05).Patients with IP showed decreased transcriptional levels of Foxp3, GITR and CTLA-4 in CD4+CD25+T cells as compared with healthy controls, but were up-regulated with the treatment of KD.The ex-pression of transcription factors including T-bet, ROR-γ, IFN-γand IL-17A in CD4+CD25-T cells in pa-tients with IP were higher than those in healthy subjects and were down-regulated after the treatment of KD (P<0.05).(2) The expression of PPAR-γat mRNA level in CD4+CD25-T and CD4+CD25+T cells were decreased in patients with IP as compared with those in heathy controls, but were increased after the treat-ment of KD (P<0.05).Correlation analysis showed that Treg cells had a positive correlation with PPAR-γ(r=0.61, P<0.05).However, the Th1 and Th17 cells were negatively correlated with PPAR-γ[Th1 (r=-0.54, P<0.05), Th17 (r=-0.64, P<0.05) ].(3) The levels of IL-17A and IFN-γin patients with IP were higher than those in healthy controls, but were decreased with KD treatment (P<0.05).The levels of COX-2 and PGF2αin plasma samples from patients with IP were higher than those in healthy controls ( P<0.05).A negative correlation was observed between COX-2 and PPAR-γ(r=-0.571, P<0.05). Moreover, PGF2αand PPAR-γhad a negative correlation as well (r=-0.586, P<0.05).Conclusion The treatment of KD might enhance the expression of PPAR-γthrough inhibiting the products of oxidative stress such as COX-2 and PGF2α, resulting in the rebalance of Th cell subsets and reduced expression of in-flammatory cytokines.