Combined administration of (L)-cystine and (L)-theanine enhances immune functions and protects against influenza virus infection in aged mice.
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-gamma ratio and gamma-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.
Takagi
Yasuhiro
Y
Division of Virology, Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, Osaka 537-0025, Japan.
Kurihara
Shigekazu
S
Higashi
Natsumi
N
Morikawa
Saeko
S
Kase
Tetsuo
T
Maeda
Akiko
A
Arisaka
Harumi
H
Shibahara
Susumu
S
Akiyama
Yukio
Y
D000375:Aging / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003553:Cystine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008809:Mice, Inbred C3H; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric
D000914:Antibodies, Viral; D005971:Glutamates; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003553:Cystine; C026166:theanine; D005978:Glutathione