Combined administration of L-cystine and L-theanine enhances immune functions and protects against influenza virus infection in aged mice

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 pro-duction, 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 anti-bodies by combined administration of L-cystine and L-theanine was seen 10 days after infection. The significantly elevated serum inter-leukin-10/interferon-γ ratio and γ-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 admin-istration 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.