Murine AIDS studies define antioxidant deficiency mechanisms

The exciting study of Allard et al (1) confirms apparently unrecognized studies of murine AIDS showing increased lipid peroxidation occurring concomitantly with reduced concentrations of antioxidant vitamins in tissue (2-4). Replacement of vitamin E reduced lipid peroxidation and immune dysfunction (2), which slowed cancer development (3), whereas vitamin A supplementation prolonged survival (5), in murine AIDS. However, ethanol consumption increased oxidation, accentuated immune dysfunction, stimulated cancer, and accelerated death during retrovirus infection (3, 6). Animal model studies (2, 3) have already answered a key question in Allard et aI's study: will supplementation with antioxidant vitamins reduce oxidative stress? The authors queried, what are "the mechanisms underlying the increased oxidative stress in the HIV population?" Retrovirus oxidation increased production of T helper 2 cell cytokines by a subset of cells, highly activated by retroviral antigens (2, 4). In murine AIDS, suppression of these cytokines by injection with a T cell receptor peptide prevented excessive oxidation, loss of vitamin E, and retrovirus-induced immune dysfunction (4) while maintaining resistance to an opportunistic pathogen (7). Murine retroviral oxidation, loss of antioxidant vitamins, and cytokine dysregulation have been prevented both by vitamin E (2) and antioxidant hormone (dehydroepiandrosterone) supplementation (8) and immunologically by direct suppression of the excessive cytokine secretion of T helper 2 cells with T cell receptor peptides (4, 7). Such knowledge from the murine AIDS model, supported by the current study in human AIDS (1), should be applied to human AIDS treatment (9). Over-thecounter antioxidant hormone or vitamin supplementation appears safe and efficacious in murine AIDS and in uninfected humans. Therefore, supplements of antioxidant honnones or vitamins should now be used to overcome antioxidant deficiencies in HIV-infected persons (9). This should help to prevent the loss of disease resistance and the resulting cytokine dysregulation due to retrovirus-induced antioxidant deficiencies, while we await confinnation of the benefits of such supplements in HIV-infected patients from clinical trials (10).