SummaryWe characterized the underlying mechanisms by which glutathione (

Cytokines are signaling biomolecules that serve as key regulators of our immune system. CD4+ T-cells can be grouped into 2 major categories based on their cytokine profile: T-helper 1 (TH1) subset and T-helper 2 (TH2) subset. Protective immunity against HIV infection requires TH1-directed CD4 T-cell responses, mediated by cytokines, such as interleukin-1β (IL-1β), IL-12, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Cytokines released by the TH1 subset of CD4 T-cells are considered important for mediating effective immune responses against intracellular pathogens such as Mycobacterium tuberculosis (M. tb). Oxidative stress and redox imbalance that occur during HIV infection often lead to inappropriate immune responses. Glutathione (GSH) is an antioxidant present in nearly all cells and is recognized for its function in maintaining redox homeostasis. Our laboratory previously reported that individuals with HIV infection have lower levels of GSH. In this study, we report a link between lower levels of GSH and dysregulation of TH1- and TH2-associated cytokines in the plasma samples of HIV-positive subjects. Furthermore, we demonstrate that supplementing individuals with HIV infection for 13 weeks with liposomal GSH (lGSH) resulted in a significant increase in the levels of TH1 cytokines, IL-1β, IL-12, IFN-γ, and TNF-α. lGSH supplementation in individuals with HIV infection also resulted in a substantial decrease in the levels of free radicals and immunosuppressive cytokines, IL-10 and TGF-β, relative to those in a placebo-controlled cohort. Finally, we determined the effects of lGSH supplementation in improving the functions of immune cells to control M. tb infection by conducting in vitro assays using peripheral blood mononuclear cells collected from HIV-positive individuals at post-GSH supplementation. Our studies establish a correlation between low levels of GSH and increased susceptibility to M. tb infection through TH2-directed response, which may be relieved with lGSH supplementation enhancing the TH1 response.

HE ADVENT OF HIGHLY ACTIVE antiretroviral therapy (HAART) dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, but limitations of HAART regimens include short plasma and intracellular half-life, drug-drug interactions, high pill burden, and adverse effects. In a metaanalysis of 23 prospective clinical trials with varied first-generation HAART regimens, suppression of HIV-1 RNA levels to less than or equal to 50 copies/mL at week 48 occurred in only 47% of treatment-naive patients. 1 Oncedaily HAART provides a strategy that should increase adherence and thereby Author Affiliations, Financial Disclosures, and Members of the FTC-301A Study Team are listed at the end of this article.

In this anonymous Web survey, which had limitations, the two species had different effect associations on symptoms and conditions, possibly because of ingredient differences. Future surveys and subsequent prospective definitive trials are needed to confirm the findings.