Glutathione and immune function

The immune system works best if the lymphoid cells have a delicately balanc ed intermediate level of glutathione. Even moderate changes in the intracel lular glutathione level have profound effects on lymphocyte functions. Cert ain functions, such as the DNA synthetic response, are exquisitely sensitiv e to reactive oxygen intermediates and, therefore, are favoured by high lev els of the antioxidant glutathione. Certain signal pathways, in contrast, a re enhanced by oxidative conditions and favoured by low intracellular gluta thione levels. The available evidence suggests that the lymphocytes from he althy human subjects have, on average, an optimal glutathione level. There is no indication that immunological functions such as resistance to infecti on or the response to vaccination may be enhanced in healthy human subjects by administration of glutathione or its precursor amino acid cysteine. How ever, immunological functions in diseases that are associated with a cystei ne and glutathione deficiency may be significantly enhanced and potentially restored by cysteine supplementation. This factor has been studied most ex tensively in the case of human immunodeficiency virus (HIV)-infected patien ts who were found to experience, on average, a massive loss of S equivalent to a net loss of approximately 4 g cysteine/d. Two randomized placebo-cont rolled trials have shown that treatment of HIV-infected patients with N-ace tylcysteine caused in both cases a significant increase in all immunologica l functions under test, including an almost complete restoration of natural killer cell activity. It remains to be tested whether cysteine supplementa tion may be useful also in other diseases and conditions that are associate d with a low mean plasma cystine level and impaired immunological functions .