Influenza infected vitamin C deficient mice have increased lung pathology and an altered immune response to influenza virus infection

Abstract

This study was designed to determine the effects of ascorbic acid deficiency on the immune response to influenza virus infection. Previous work in our laboratory has demonstrated that the antioxidant nutrients selenium and vitamin E are important mediators of the immune response to infection. Because one of the functions of vitamin C is as an antioxidant, we tested whether vitamin C could impact the immune response and/or lung pathology following influenza virus infection. L-gulono-γ-lactone oxidase gene inactivated mice (gulo −/− mice) require L-ascorbic acid supplementation in their drinking water for survival. Five-week old male and female gulo−/ − mice were provided with water or water containing 330 mg/mL ascorbic acid for three weeks prior to inoculation with influenza A/Bangkok/1/79. There were no differences in influenza lung titers between supplemented and unsupplemented groups, however lung pathology in the vitamin C deficient mice was decreased on days 1 and 3 post infection, but increased at day 7 compared with vitamin C sufficient mice. There was a gender difference on the effect of ascorbic acid on the immune response: male vitamin C deficient mice had a decreased expression of mRNA for RANTES, IL-1β and TNF-α in the lungs at 24 hours post-infection. However, 3 days post infection vitamin C deficient male mice had an increased expression of RANTES, MCP-1 and IL-12. None of these differences were observed in female vitamin C deficient mice. These data suggest that ascorbic acid is required for limiting lung pathology post infection and can influence the immune response. Supported by NIH grant R01 AI055050