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

Background: To facilitate the evaluation of vitamin E (α-tocopherol, αT) status on health outcomes, the αT transfer protein knockout (Ttpa ^-/- ) mouse model has proved to be an effective tool for lowering αT 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 αT-deficient diet feeding period but did not find a difference in LPS-induced inflammatory 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 αT-deficient diet altered the inflammatory response 4 and/or 24 h after LPS injection in WT and Ttpa ^-/- mice.

Methods: WT and Ttpa ^-/- weanling littermates were fed an αT-deficient diet ad libitum for 12 wk. Mice were then injected with LPS (10 μg/mouse) or saline (control) intraperitoneally and killed 4 (Study 1) or 24 h (Study 2) later. Concentrations of αT 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 responses was examined via RT-PCR.

Results: αT concentrations in the brain, liver, and serum of Ttpa ^-/- mice were notably lower or undetectable compared with WT mice in both studies. Hepatic αT 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 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 response. At 24 h post-dosing, there was a partial, transitory recovery response in both Ttpa ^-/- and WT mice.