Characterizing the Effects of Glutathione as an Immunoadjuvant in the Treatment of Tuberculosis

Abstract

Mycobacterium tuberculosis is the etiological agent that is responsible for causing tuberculosis (TB), which continues to affect millions of people worldwide, and the rate of resistance of M. tuberculosis to antibiotics is ever increasing. We tested the synergistic effects of N-acetyl cysteine (NAC; the precursor molecule for the synthesis of glutathione [GSH]) and individual first-line antibiotics typically given for the treatment of TB, such as isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA), to improve the ability of macrophages to control intracellular M. tuberculosis infection.

Cyclic Peptide [R4W4] in Improving the Ability of First-Line Antibiotics to Inhibit Mycobacterium tuberculosis Inside in vitro Human Granulomas

“…Therefore, higher amounts of the IFNγ release may therefore serve as an additional effector mechanism by which in vitro granulomas treated with 4 µg/ml of [R 4 W 4 ] control M. tb infection. IL-10 is an immune-suppressive cytokine that can inhibit phagosome-lysosome fusion and dampen other effector responses against M. tb infection (11,(22)(23)(24). We observed a notable decrease in the levels of IL-10 in [R 4 W 4 ]-treated granulomas at both concentrations (4 and 8 µg/ml).…”

“…downregulate the effector functions of macrophage against M. tb infection (11,(22)(23)(24)34). Therefore, combination of [R 4 W 4 ] with INH can downregulate oxidative stress and production of TNF-α and IL-10, which in turn can favor improved control of M. tb infection when compared to treatment with INH alone.…”

N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis

“…NAC demonstrated antimycobacterial properties in previous studies of different models [9][10][11]. NAC cleared mycobacteria through several mechanisms including immunomodulation [12], enhancement of GSH level [13], and direct antimycobacterial effects [14].…”

“…Moreover, NAC modulated immunity against tuberculosis where it increased interleukin-2 (IL-2), IL-12, and interferon gamma (INF-γ) production [9,20,24] and these cytokines are important for suppressing mycobacterial proliferation. Additionally, NAC reduced the production of IL-10, a cytokine that favors mycobacterial proliferation [10,11]. The antioxidant also reduced the proinflammatory cytokines such as IL-1, IL-6, and tumor necrosis factor alpha (TNF-α), cytokines known to exacerbate oxidative stress.…”

“…Anti-TB Drugs. NAC showed additive/synergistic antimycobacterial interaction with all first-line and some second-line anti-TB drugs [10,24,30]. Administration of NAC and suboptimal concentrations of isoniazid (INH) or rifampicin (RIF) to peripheral blood mononuclear 2…”