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.