Glutathione and lymphocyte activation: a function of ageing and auto-immune disease

A decline in tissue and serum of glutathione (GSH) content and GSH-metabolizing enzymes with age has been implicated in the increasing susceptibility to carcinogens, disease and drugs which occurs with advanced age. Immunological senescence has been directly associated with increased incidence of cancer and infection with age. The auto-immune diseases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) demonstrate depressed T-cell function together with B-cell hyperactivity. In addition, RA and SLE are chronic inflammatory conditions which have been associated with low serum and erythrocyte GSH concentrations when compared to normal. We hypothesized that augmentation of intracellular GSH concentrations in lymphocytes may enhance immune function in depressed immune states. Our data, using murine animal models for ageing (C57BL/6J) and the RA/SLE-like auto-immune diseases of the MRL/lpr mouse, indicate that intracellular glutathione of splenic lymphocytes does not decline with age or with a chronic inflammatory auto-immune disease. In contrast, immune responsiveness in splenic lymphocytes does decline. We can, however, augment both intracellular GSH concentrations and the immune response of splenic lymphocytes from animals of all ages as well as in those animals with the SLE-like auto-immune disease.