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Nutritional Immunology

-Tocopherol and Selenium Facilitate Recovery from Lipopolysaccharide-Induced Sickness in Aged Mice^1,2

Brian M. Berg^*,3, Jonathan P. Godbout^*,, Jing Chen, Keith W. Kelley^*, and Rodney W. Johnson^*,,4

^* Division of Nutritional Sciences and Department of Animal Sciences, University of Illinois, Urbana, IL 61801

⁴To whom correspondence should be addressed. E-mail: rwjohn{at}uiuc.edu.

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 -tocopherol (-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 -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 40% reductions due to LPS treatment. Mice fed the low diet had greater LPS-induced weight loss than mice fed the high diet. Plasma -T concentration and glutathione peroxidase (GPX) activity increased with each increment in -T and selenium 24 h post-LPS treatment. Brain -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-1ß, and tumor necrosis factor (TNF) mRNA levels were elevated by LPS 3-fold in cortex, cerebellum, striatum, and hippocampus. Thus, antioxidants inhibit sickness behavior independently of IL-6, IL-1ß, and TNF mRNA levels 2 h post-LPS in the brain regions analyzed. Taken together, these findings suggest that adequate intake of dietary -T and selenium may help promote recovery from gram-negative bacterial infection in the aged.

KEY WORDS: • aging • cytokines • sickness behavior • vitamin E • selenium

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