α-Tocopherol Transfer Protein-Null Mice with Very Low α-Tocopherol Status Do Not Have an Enhanced Lipopolysaccharide-Induced Acute Inflammatory Response

Background: The alpha-tocopherol transfer protein-null (Ttpa-/-) mouse model is a valuable tool for studying the molecular and functional consequences of vitamin E (alpha-tocopherol, alpha T) deficiency. Because alpha T has been associated with reduced oxidative stress and improved immune function, we hypothesized that depleted alpha T concentration would exacerbate LPS-induced acute inflammatory response in the brain and heart of Ttpa-/-mice fed a vitamin E deficient (VED) diet. Objectives: The objective was to investigate how extremely low alpha T status, followed by exposure to LPS, altered the acute inflammatory response to LPS in Ttpa-/-and wild-type (Ttpa+/+) mice. Methods: Three-week-old male Ttpa+/+ and Ttpa-/-littermates (n = 36/genotype) ingested a VED diet ad libitum for 4 wk. At week 7, mice received an intraperitoneal LPS (1 or 10 mu g/mouse) or saline (control) injection and were killed 4 h postinjection. Brain and heart IL-6 protein concentrations and tissue and serum alpha T concentrations were measured via ELISA and HPLC with photodiode array detection, respectively. Hippocampal Il-6, Tnf, and Gpx1 gene expression were measured via reverse transcriptase-quantitative polymerase chain re -action, and blood immune cell profiles were measured via a hematology analyzer. Results: alpha T accumulation in analyzed tissues and serum of Ttpa-/-mice was substantially lower than Ttpa+/+ mice. Circulating white blood cell concentration, particularly lymphocytes, were lower in all LPS groups compared with controls (P < 0.01). The 10 mu g LPS groups had elevated IL-6 in the cerebellum and heart compared with controls, confirming an acute inflammatory response (P < 0.01). Hippocampal and heart Il-6 gene expression in the LPS-treated Ttpa-/-mice was upregulated in a dose-dependent manner (P < 0.05). Conclusions: The 10 mu g LPS dose enhanced inflammatory markers in the brain, heart, and serum in each genotype but the lower alpha T status in Ttpa-/-mice did not further impact the acute immune responses. Curr Dev Nutr 20xx;xx.