α-Tocopherol attenuates lipopolysaccharide-induced sickness behavior in mice

Antioxidants protect cells from oxidative damage and reduce lipopolysaccharide (LPS)-induced expression of inflammatory cytokines. Because inflammatory cytokines induce sickness behavior, we hypothesized that antioxidants, namely α-tocopherol (α-T) and selenium would inhibit sickness behavior caused by LPS. In an initial study, mice were injected intraperitoneal (i.p.) with vehicle, 2, or 20mg α-T for 3 consecutive days and then challenged with vehicle, 1, 10, or 100μg of LPS. Sickness behavior was quantified by measuring social exploratory behavior. Vehicle pretreated mice injected with LPS showed a marked reduction in social behavior at 4h (p<.01). However, sickness behavior induced by the lowest dose of LPS was partially or completely blocked by 2 or 20mg α-T, respectively. α-T did not prevent sickness from higher doses of LPS. In a second study, mice were fed AIN93-M modified diets containing 10, 75, and 500mg α-T/kg and 0.05, 0.15, and 2mg selenium/kg for 8 weeks and then challenged with saline or LPS (1μg). The highest concentration of dietary α-T and selenium tended (p=.1) to reduce LPS-induced sickness behavior. Mice fed diets low in antioxidants had reduced plasma α-T levels and glutathione peroxidase activity (p=.08 and p<.01, respectively) and elevated liver thiobarbituric acid reactive substances (p<.001) 24h post LPS. Collectively, these data indicate that α-T improved the oxidative status after exposure to LPS, which may explain its ability to ameliorate symptoms of sickness.