Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice

J Nutr. 2006 Oct;136(10):2611-6. doi: 10.1093/jn/136.10.2611.


This study was designed to determine the effects of vitamin C deficiency on the immune response to infection with influenza virus. l-Gulono-gamma-lactone oxidase gene-inactivated mice (gulo-/- mice) require vitamin C supplementation for survival. Five-wk-old male and female gulo-/- mice were provided water or water containing 1.67 mmol/L vitamin C for 3 wk before inoculation with influenza A/Bangkok/1/79. There were no differences in lung influenza virus titers between vitamin C-adequate and -deficient mice; however, lung pathology in the vitamin C-deficient mice was greater at 1 and 3 d after infection but less at d 7 compared with vitamin C-adequate mice. Male vitamin C-deficient mice had higher expression of mRNA for regulated upon activation normal T expressed and secreted (RANTES), IL-1beta, and TNF-alpha in the lungs at d 1 after infection compared with male controls. However, at d 3 after infection, male vitamin C-deficient mice had less expression of mRNA for RANTES, monocyte chemotactic protein-1 (MCP-1), and IL-12 compared with male controls. None of these differences were observed in female mice. Vitamin C-deficient male mice also had greater nuclear factor-kappaB activation as early as 1 d after infection compared with male controls. These data suggest that vitamin C is required for an adequate immune response in limiting lung pathology after influenza virus infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Ascorbic Acid / analysis
  • Ascorbic Acid Deficiency / pathology*
  • Ascorbic Acid Deficiency / virology
  • Chemokine CCL2 / genetics
  • Chemokine CCL5 / genetics
  • Gene Expression
  • Glutathione / analysis
  • Influenza A virus*
  • Interleukin-1 / genetics
  • L-Gulonolactone Oxidase / deficiency*
  • L-Gulonolactone Oxidase / genetics
  • L-Gulonolactone Oxidase / physiology
  • Lung / chemistry
  • Lung / pathology*
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / analysis
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology*
  • Oxidation-Reduction
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / genetics


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL5
  • Interleukin-1
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • L-Gulonolactone Oxidase
  • Glutathione
  • Ascorbic Acid