Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice.
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.
Li
Wei
W
Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
Maeda
Nobuyo
N
Beck
Melinda A
MA
D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis; D001206:Ascorbic Acid Deficiency / Q000473:pathology* / Q000821:virology; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D015870:Gene Expression; D005978:Glutathione / Q000032:analysis; D009980:Influenza A virus; D007375:Interleukin-1 / Q000235:genetics; D050544:L-Gulonolactone Oxidase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008168:Lung / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000032:analysis; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D050544:L-Gulonolactone Oxidase; D005978:Glutathione; D001205:Ascorbic Acid