Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection

Abstract

L-ascorbic acid (vitamin C) is one of the well-known anti-viral agents, especially to influenza virus. Since the in vivo anti-viral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-α/β, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-α/β, were increased in the lung. Taken together, vitamin C shows in vivo anti-viral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-α/β.

Protective Activity of Ascorbic Acid at Influenza Infection

“…In contrast, on late stages the levels of RANTES, MCP-1 and IL-12 were lower than in control mice [38]. In another similar study [36], it was shown that viral activity in the lung tissue of Gulo (-/-) mice was increased in the absence of AA, and the production of the antiviral cytokine IFNα/β was lower than in animals receiving AA. The level of cellular infiltration and the production of pro-inflammatory cytokines, such as TNFα and IL-1α/β in lung tissue, were increased.…”

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome

“…The neutrophil phagocytic activity and oxidative death were also enhanced [95][96][97]. Lymphocyte proliferation was also accelerated [95][96][97].…”

“…In general, Ascorbic acid is concentrated in leucocytes, lymphocytes, and macrophages [93,94]. Chemotaxis was improved by Vit-C [95][96][97]. The neutrophil phagocytic activity and oxidative death were also enhanced [95][96][97].…”

Vitamin C Deficiency Causes Severe Defects in the Development of the Neonatal Cerebellum and in the Motor Behaviors ofGulo−/−Mice

“…Thus, Gulo -/ -mice are useful to investigate the in vivo effect of vitamin C because they are unable to synthesize vitamin C and exhibit physiological responses that resemble those in vitamin C-deficient humans. We have recently reported on the regulatory role of vitamin C in the inflammation of the liver and heart, as well as on the viral infection of vitamin C-deficient Gulo -/ -mice (2,25,29). We have also found a preferential accumulation and maintenance of vitamin C in the brain.…”