title: Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals.
abstract: 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.
authors.affiliation: 1 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California.|2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: Judy
authors.initials: J
authors.lastname: Ly
authors.affiliation: 1 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California.|2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: Minette
authors.initials: M
authors.lastname: Lagman
authors.affiliation: 1 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California.
authors.forename: Tommy
authors.initials: T
authors.lastname: Saing
authors.affiliation: 1 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California.|2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: Manpreet Kaur
authors.initials: MK
authors.lastname: Singh
authors.affiliation: 1 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California.|2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: Enrique Vera
authors.initials: EV
authors.lastname: Tudela
authors.affiliation: 2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: Devin
authors.initials: D
authors.lastname: Morris
authors.affiliation: 2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: Jessica
authors.initials: J
authors.lastname: Anderson
authors.affiliation: 2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: John
authors.initials: J
authors.lastname: Daliva
authors.affiliation: 3 Western Diabetes Institute , Pomona, California.
authors.forename: Cesar
authors.initials: C
authors.lastname: Ochoa
authors.affiliation: 3 Western Diabetes Institute , Pomona, California.
authors.forename: Nishita
authors.initials: N
authors.lastname: Patel
authors.affiliation: 4 Center for Comparative Effectiveness and Outcomes Research, Loma Linda University , Loma Linda, California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pearce
authors.affiliation: 1 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California.|2 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, California.
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Venketaraman
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000096:biosynthesis*; D004337:Drug Carriers / Q000627:therapeutic use; D005978:Glutathione / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D053765:Interleukin-12 Subunit p35 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008081:Liposomes / Q000627:therapeutic use; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D000975:Antioxidants; D016207:Cytokines; D004337:Drug Carriers; C508858:IL12A protein, human; C508585:IL1B protein, human; D053765:Interleukin-12 Subunit p35; D053583:Interleukin-1beta; D008081:Liposomes; D017382:Reactive Oxygen Species; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005978:Glutathione