May 2023
Arbi Abnousian, Joshua Vasquez, Kayvan Sasaninia, Melissa Kelley, and Vishwanath Venketaraman

 

Abstract

Glutathione (GSH) is an antioxidant in human cells that is utilized to prevent damage occurred by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals. Due to its immunological role in tuberculosis (TB), GSH is hypothesized to play an important part in the immune response against M. tb infection. In fact, one of the hallmark structures of TB is granuloma formation, which involves many types of immune cells. T cells, specifically, are a major component and are involved in the release of cytokines and activation of macrophages. GSH also serves an important function in macrophages, natural killer cells, and T cells in modulating their activation, their metabolism, proper cytokine release, proper redox activity, and free radical levels. For patients with increased susceptibility, such as those with HIV and type 2 diabetes, the demand for higher GSH levels is increased. GSH acts as an important immunomodulatory antioxidant by stabilizing redox activity, shifting of cytokine profile toward Th1 type response, and enhancing T lymphocytes. This review compiles reports showing the benefits of GSH in improving the immune responses against M. tb infection and the use of GSH as an adjunctive therapy for TB.

Keywords: glutathione, tuberculosis, mycobacteria, interferons, interleukins, tumor necrosis factor, transforming growth factor

 

Conclusions

Adequate GSH levels and balanced levels of free radicals are important for an effective immune response against a vast number of infections. Specifically, TB is endemic and one of the leading causes of death in every part of the world. Through research and experiments, our growing understanding of TB and patients’ responses to treatments has improved and increased the number of available therapy options for TB patients. M. tb infection causes a cytokine imbalance and changes the balance of free radicals by causing oxidative stress. One molecule that has shown promising results for treatment of TB is GSH. GSH, in addition to other treatment options, such as Th1 cytokines, everolimus, and first-line antibiotics, such as rifampin, show significant improvements in the levels of GSH, free radicals, and cytokine profile. We have also highlighted the importance of GSH for patients with HIV or type 2 diabetes, who are more susceptible to TB. These individuals have increased pro-inflammatory cytokines in their bodies leading to more oxidative stress and generation of free radicals. Therefore, GSH can play a role in creating a balanced redox activity. GSH is a naturally synthesized molecule by our body’s cells that shifts the immune response toward a beneficial state and should be a part of an adjunctive therapy against TB.