Combined Administration L-Cystine and L-Theanine Enhances Immune Functions and Protects against Influenza Virus Infection in Aged Mice

Abstract

ABSTRACT. Cell-mediated and humoral immune responses are attenuated with aging. Intracellular glutathione (GSH) levels also decrease with aging. Previously, we have reported that combined administration of L -cystine and L -theanine enhances antigen-specific IgG production, partly through augmentation of GSH levels and T helper 2-mediated responses in 12-week-old mice. These findings suggest that combined administration of L -cystine and L -theanine to aged mice improves immune responses via increase of GSH synthesis. Here, we examined the effects of combined administration of L -cystine and L -theanine on antigen-specific antibody production and influenza virus infection in aged mice. Combined administration of these amino acids for 14 days before primary immunization significantly enhanced the serum antigen-specific IgM and IgG levels in 24-month-old mice. Furthermore, 13-month-old mice co-treated with these amino acids orally for 10 days had significantly lower lung viral titers than controls at 6 days after influenza virus infection. In addition, this co-treatment also significantly prevented the weight loss associated with infection. Enhancement of anti-influenza-virus IgG antibodies by combined administration of L -cystine and L -theanine was seen 10 days after infection. The significantly elevated serum interleukin-10/interferon- ratio and -glutamylcysteine synthetase mRNA expression, which is the rate-limiting enzyme of GSH synthesis, in the spleen 3 days after infection may have contributed to the observed beneficial effects. These results suggest that combined administration of L -cystine and L -theanine enhances immune function and GSH synthesis which are compromised with advanced age, and may become a useful strategy in healthy aging. With aging, the human body's defense capability weakens, including production of antibodies and cytotoxic T lymphocytes (CTL) and cellular immune function [12,28]. These age-related alterations seem to result from oxidative stress [9]. Diet supplementation with antioxidants has been used to prevent or delay the onset of age-related immune impairment [7]. For example, a diet that contains the antioxidant 2-mercaptoethanol, which reduces cystine to cysteine and increases the intracellular concentration of glutathione (GSH; L --glutamyl-L -cysteinyl-glycine), improves several types of immune response in aged mice [17]. Dietary supplementation with GSH, another antioxidant, has also been shown to increase cell-mediated immunity in aged mice [11]. In addition, GSH levels and the gene expression of -glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis, are known to decrease with aging [24]. These results suggest that GSH antioxidant therapy may aid in preventing or delaying the onset of age-related immune impairment.A recent study we performed indicated that combined administration of L -cystine and L -theanine (-glutamylethylamide, a specific amino acid found in green tea) to young mice increases the GSH level in the liver and also enhances the s...

γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells

“…Inducers of GCS, such as treatments with sulfoximine and partial hepatomy, also induce GSS expression in rat and human hepatocytes, and induction of both GSS expression and GSH synthesis occurs simultaneously (Huang et al 2000;Huang et al 2001). In addition, exogenous substrates for GSH synthesis are more effective when GSH are depleted after viral infection, but not before the infection or under normal conditions (Takagi et al 2010). Moreover, induction of both GSS gene expression and GSH levels was observed with increased TBARS levels in ApoE−/− mice fed folate and vitamin E deficient diets (Tchantchou et al 2004).…”

“…Therefore, we currently investigate a role of GGC as a cell-penetrating pepide by assessing its cellular uptake using an animal model. Administration of dipeptides influence atherosclerotic development in apo E-deficient mouse models (Matsui et al 2010) and immune responses and mRNA expression of GCS-HS in both humans and mice with compromised immune functions (Murakami et al 2009;Takagi et al 2010). Oligopeptides inhibit TNFα-induced activation of NF-κB in human aortic endothelial cells (Ringseis et al 2009) and ROS formation by inducing the expression of antioxidant enzymes, superoxide dismutase (SOD) and heme oxygenase, in mice (White et al 2009).…”

Health Benefits of Theanine in Green Tea: A Review

“…Co-administration of Ltheanine with L-cystine enhances levels of serum IgG and antigen-specific IgM [52]. In addition, oral administration with L-theanine and L-cystine before vaccination can enhance the immune response to influenza vaccine in elderly persons with low haemoglobin [53].…”

Progress in the research of GSH in cells

“…protect against infection. For example, L-cysteine can increase GSH synthesis and the subsequent increases in GSH levels can enhance the defense against influenza virus infection [47].…”