alpha-Tocopherol and selenium facilitate recovery from lipopolysaccharide-induced sickness in aged mice

J Nutr. 2005 May;135(5):1157-63. doi: 10.1093/jn/135.5.1157.


The elderly suffer a decline in immune function that increases their vulnerability to infections. Because antioxidants improve some age-related deficits in immune and cognitive function, our goal was to determine whether dietary alpha-tocopherol (alpha-T) and selenium inhibit LPS-induced sickness behavior in aged mice. Male BALB/c mice were fed modified AIN93-M diets that were low, adequate, or high in both alpha-T (10, 75, or 500 mg/kg) and selenium (0.05, 0.15, or 2 mg/kg) from 18 to 21 mo of age. Sickness was quantified by measuring time in social exploration of a novel juvenile conspecific. The lipopolysaccharide treatment reduced social exploration by 74% at 2 h, regardless of diet. By 4 h, aged mice fed the low diet were 88% less social, whereas mice fed the adequate and high diets displayed only approximately 40% reductions due to LPS treatment. Mice fed the low diet had greater LPS-induced weight loss than mice fed the high diet. Plasma alpha-T concentration and glutathione peroxidase (GPX) activity increased with each increment in alpha-T and selenium 24 h post-LPS treatment. Brain alpha-T concentration and GPX activity were lower in mice fed the low diet than in those fed the adequate or high diet. Regardless of diet, interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF)alpha mRNA levels were elevated by LPS approximately 3-fold in cortex, cerebellum, striatum, and hippocampus. Thus, antioxidants inhibit sickness behavior independently of IL-6, IL-1beta, and TNFalpha mRNA levels 2 h post-LPS in the brain regions analyzed. Taken together, these findings suggest that adequate intake of dietary alpha-T and selenium may help promote recovery from gram-negative bacterial infection in the aged.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging
  • Animals
  • Brain / enzymology
  • Diet
  • Disease Models, Animal
  • Escherichia coli Infections / drug therapy*
  • Exploratory Behavior
  • Gene Expression Regulation / drug effects
  • Glutathione Peroxidase / blood
  • Glutathione Peroxidase / metabolism
  • Interleukin-6 / blood
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Polymerase Chain Reaction
  • Selenium / therapeutic use*
  • alpha-Tocopherol / therapeutic use*


  • Interleukin-6
  • Lipopolysaccharides
  • Glutathione Peroxidase
  • alpha-Tocopherol
  • Selenium