Direct effects of glutathione

One of the first indications that glutathione influences aspects of immune function that are related to T lymphocytes came from a study in which the GSH content of lymphocytes was measured in a group of healthy volunteers (Kinscherf et al., 1994). The numbers of helper (CD4+) and cytotoxic (CD8+) T-cells increased in parallel with intracellular glutathione concentrations up to 30 nmol mg-1 protein. However, the relationship between cellular glutathione concentrations and cell numbers was complex, with numbers of both subsets declining at intracellular glutathione concentrations between 30 and 50 nmol mg-1 protein. The study also revealed that cell numbers were responsive to long-term changes in GSH content. When the subjects engaged in a programme of intensive physical exercise daily for 4 weeks, a fall in glutathione concentrations occurred. Individuals with glutathione concentrations in the optimal range before exercise who experi enced a fall in concentration after exercise showed a 30% fall in CD4+ T-cell numbers. The decline in T-cell number was prevented by administration of N-acetyl-cysteine (NAC) (this is metabolized to cysteine (see later)). This study suggests that immune cell function may be sensitive to a range of intracellular sulphydryl compounds, including glutathione and cysteine. In HIV+ individuals and patients with acquired immune deficiency syndrome (AIDS), a reduction in cellular and plasma glutathione has been noted (Staal et al., 1992). It is unclear at present whether the depletion in lymphocyte population that occurs in these subjects is related to this phenomenon. However, in a large, randomized, doubleblind, placebo-controlled trial, administration of 600 mg day-1 of NAC for 7 months resulted in both anti-inflammatory and immunoenhancing effects (Breitkreutz et al., 2000). A decrease in plasma IL-6 concentration occurred, together with an increase in lymphocyte count and in the stimulation index of T lymphocytes in response to tetanus toxin. The precise mechanism underlying the complex effects of changes in cellular glutathione content are not clear, and whether they are related to GSH function as an antioxidant or to some other property is not apparent. However, a recent study suggests that glutathione promotes IL-12 production by antigen-presenting cells, so driving T-helper (Th) cells along the Th1 pathway of differentiation (Peterson et al., 1998).

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