High dietary vitamin C intake reduces glucocorticoid-induced immunosuppression and measures of oxidative stress in vitamin C-deficient senescence marker protein 30 knockout mice

• Published in: British journal of nutrition Vol. 122; no. 10; pp. 1120 - 1129
• Main Authors: Uchio, Ryusei, Hirose, Yoshitaka, Murosaki, Shinji, Ishigami, Akihito
• Format: Journal Article
• Language: English
• Published: England Cambridge University Press 28.11.2019
• Subjects: Antioxidants; Ascorbic acid; CD8 antigen; Cell proliferation; Dexamethasone; Diet; Dietary intake; Glucocorticoids; Glutathione; Immunosuppression; Interferon; Interleukin 12; Interleukin 2; Intracellular; Intracellular levels; Kinases; Lymphocytes; Lymphocytes T; Markers; Nutrient deficiency; Oxidative stress; Proteins; Rodents; Senescence; Splenocytes; Steroids; Superoxide dismutase; Thiobarbituric acid; Vitamin C; γ-Interferon; Japan; Oxidative stress; Immune function; Glucocorticoids; SMP30-KO mice; Vitamin C
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/s0007114519001922

Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. The present study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg per d; 0·02 %VC group) or a high VC content (200 mg/kg per d; 0·2 %VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02 %VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2 %VC group compared with the other two groups. In the 0·02 %VC and wild-type groups, dexamethasone caused a significant decrease in the cluster of differentiation (CD)4+ and CD8+ T cells among splenocytes as well as a significant decrease in IL-2, IL-12p40 and interferon-γ protein production by splenocytes and a significant decrease in T-cell proliferation among splenocytes. In the 0·2 %VC group, these dexamethasone-induced immunosuppression improved when compared with the other two groups. In addition, reduction in the intracellular levels of ascorbic acid, superoxide dismutase and glutathione in splenocytes by dexamethasone as well as elevation in thiobarbituric acid-reactive substances were significantly suppressed in the 0·2 %VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T-cell dysfunction by maintaining intracellular antioxidant activity.