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

Antimicrob Agents Chemother. 2018 Oct 24;62(11):e01132-18. doi: 10.1128/AAC.01132-18. Print 2018 Nov.

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. GSH, a pleiotropic antioxidant molecule, has previously been shown to display both antimycobacterial and immune-enhancing effects. Our results indicate that there was not only an increase in beneficial immunomodulatory effects but also a greater reduction in the intracellular viability of M. tuberculosis when macrophages were treated with the combination of antibiotics (INH, RIF, EMB, or PZA) and NAC.

Keywords: Mycobacterium tuberculosis; additive effects; cytokines; glutathione; macrophages; synergistic effects; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Antitubercular Agents / pharmacology
  • Cell Line
  • Drug Therapy, Combination / methods
  • Ethambutol / pharmacology
  • Glutathione / pharmacology*
  • Humans
  • Isoniazid / pharmacology
  • Microbial Sensitivity Tests / methods
  • Mycobacterium tuberculosis / drug effects
  • Pyrazinamide / pharmacology
  • Rifampin / pharmacology
  • THP-1 Cells / drug effects
  • Tuberculosis / drug therapy*
  • Tuberculosis, Multidrug-Resistant / drug therapy

Substances

  • Adjuvants, Immunologic
  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Pyrazinamide
  • Ethambutol
  • Glutathione
  • Isoniazid
  • Rifampin