Alpha-tocopherol attenuates lipopolysaccharide-induced sickness behavior in mice

Brain Behav Immun. 2004 Mar;18(2):149-57. doi: 10.1016/S0889-1591(03)00113-2.


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 alpha-tocopherol (alpha-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 alpha-T for 3 consecutive days and then challenged with vehicle, 1, 10, or 100 microg 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 alpha-T, respectively. alpha-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 500 mg alpha-T/kg and 0.05, 0.15, and 2mg selenium/kg for 8 weeks and then challenged with saline or LPS (1 microg). The highest concentration of dietary alpha-T and selenium tended (p = .1) to reduce LPS-induced sickness behavior. Mice fed diets low in antioxidants had reduced plasma alpha-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 alpha-T improved the oxidative status after exposure to LPS, which may explain its ability to ameliorate symptoms of sickness.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animal Feed
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Behavior, Animal / drug effects*
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Exploratory Behavior / drug effects*
  • Glutathione Peroxidase / drug effects
  • Lipid Peroxidation / drug effects
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Selenium / pharmacology
  • Social Behavior
  • alpha-Tocopherol / administration & dosage*


  • Antioxidants
  • Lipopolysaccharides
  • Glutathione Peroxidase
  • alpha-Tocopherol
  • Selenium