The Impact of LPS on Inflammatory Responses in Alpha-Tocopherol Deficient Mice

Background: To facilitate the evaluation of vitamin E (alpha-tocopherol, alpha-tocopherol, alpha T) status on health outcomes, the alpha T transfer protein knockout (Ttpa- - - ) mouse model has proved to be an effective tool for lowering alpha T body stores. Our previous study showed a further reduction in grip strength in LPS-treated Ttpa- - - - compared with wild-type (WT) mice during a 9-wk alpha T-de fi cient diet feeding period but did not fi nd a difference in LPS-induced inflammatory fl ammatory response markers. Further optimization of this mouse model is warranted to determine the appropriate depletion period and biomarkers endpoints. Objectives: The objective was to examine whether 12 wk of an alpha T-de fi cient diet altered the inflammatory fl ammatory response 4 and/or 24 h after LPS injection in WT and Ttpa- - - mice. Methods: WT and Ttpa- - - - weanling littermates were fed an alpha T-de fi cient diet ad libitum for 12 wk. Mice were then injected with LPS (10 mu g/ mouse) or saline (control) intraperitoneally and killed 4 (Study 1) or 24 h (Study 2) later. Concentrations of alpha T in tissues were measured via HPLC. Grip strength and burrowing were evaluated to assess sickness behaviors before/after LPS injection. Expression of genes related to inflammatory fl ammatory responses was examined via RT-PCR. Results: alpha T concentrations in the brain, liver, and serum of Ttpa- - - mice were notably lower or undetectable compared with WT mice in both studies. Hepatic alpha T concentrations were further decreased 24 h after LPS injection. Grip strength was reduced at 4 h post-injection but partially recovered to baseline values 24 h after LPS injection. The expression of genes related to inflammatory fl ammatory responses were altered by LPS. However, neither measure of sickness behavior nor gene expression markers differed between genotypes. Conclusions: A 4-h LPS challenge reduced grip strength and resulted in an inflammatory fl ammatory response. At 24 h post-dosing, there was a partial, transitory recovery response in both Ttpa- - - and WT mice.