Glutathione Depletion in Rats Impairs T-Cell and Macrophage Immune Function

Abstract

Critical illness is associated with both immunosuppression and glutathione deficiency. We determined if in vivo depletion of glutathione would adversely affect immune status. Rats with normal glutathione levels and those with glutathione stores depleted by diethyl maleate underwent analysis of splenocyte function and mesenteric lymph node lymphocyte function. Lymphocytes of the spleen and mesenteric lymph nodes were tested for concanavalin A proliferative response and interleukin 2 production. Tumor necrosis factor and interleukin 6 secretion by splenic adherent cells was also measured. Glutathione-depleted animals had significantly decreased lymphocyte proliferation and decreased production of tumor necrosis factor and interleukin 6 but unaltered interleukin 2 production. These findings indicate that in vivo glutathione deficiency impairs macrophage and T-cell function. Because glutathione depletion may occur in sepsis, trauma, and shock, treatments that help maintain glutathione levels may enhance immunocompetence and thus improve the ability of patients to recover from critical illness.

The Role of Low Molecular Weight Thiols in T Lymphocyte Proliferation and IL-2 Secretion

“…antioxidants, inhibitors of GSH synthesis, and measurement of intracellular thiols. GSH has been suggested to regulate lymphocyte proliferation based on the observations that BSO-induced depletion of GSH results in the inhibition of the T cell proliferative response (4,5,7,19,28). Our study demonstrated that GSH is rate limiting for T cell proliferation only in the absence of exogenous small m.w.…”

“…NAC was found to increase IL-2 production in human peripheral blood T cells (17), as well as IL-6 production in Jurkat T cells (18). In vivo, GSH depletion in rats showed that GSH-deficient animals underwent a significantly decreased production of IL-6 and TNF-␣ (19). Furthermore, depletion of GSH was found to be associated with a reduced number of activated human T cells, as characterized by CD25 and CD69 surface markers, relative to cells with high GSH content (20).…”

The effect of vitamin C on amiodarone-induced toxicity in rat thymocytes

“…Glutathione is the major low molecular weight antioxidant in cells, and its levels often decrease during oxidative stress. Robinson et al [25] demonstrated impaired T cell and macrophage immune function in rats upon glutathione depletion. Taken together with our results, it seems that exposure of thymocytes to AMD leads to reduction of intracellular glutathione content, which may have an important role in development of oxidative stress and resulting cytotoxicity.…”

Green tea: protective action against oxidative damage induced by xenobiotics

“…Further, the lymphocyte membrane contains cholinergic receptors as well as GGT, which play an important role in the metabolism of xenobiotics such as malathion [132,137]. Erythrocytes and lymphocytes have a variety of redox systems among which glutathione (GSH) is important [132,138].…”