RESUMEN
Glutathione (GSH) is an important intracellular antioxidant responsible for neutralizing reactive oxygen species (ROS). Our laboratory previously demonstrated that the oral administration of liposomal GSH improves immune function against mycobacterium infections in healthy patients along with patients with HIV and Type 2 diabetes. We aim to determine if the topical application of a glutathione-cyclodextrin nanoparticle complex (GSH-CD) confers a therapeutic effect against mycobacterium infections. In our study, healthy participants received either topical GSH-CD (n = 15) or placebo (n = 15) treatment. Subjects were sprayed four times twice a day for three days topically on the abdomen. Blood draws were collected prior to application, and at 1, 4, and 72 h post-initial topical application. GSH, malondialdehyde (MDA), and cytokine levels were assessed in the processed blood samples of study participants. Additionally, whole blood cultures from study participants were challenged with Mycobacterium avium (M. avium) infection in vitro to assess mycobacterium survival post-treatment. Topical GSH-CD treatment was observed to elevate GSH levels in peripheral blood mononuclear cells (PBMCs) and red blood cells and decrease MDA levels in PBMCs 72 h post-treatment. An increase in plasma IL-2, IFN-γ, IL-12p70, and TNF-α was observed at 72 h post-topical GSH-CD treatment. Enhanced mycobacterium clearance was observed at 4 h and 72 h post-topical GSH-CD treatment. Overall, topical GSH-CD treatment was associated with improved immune function against M. avium infection. The findings of this pilot study suggest GSH-cyclodextrin complex formulation can be used topically as a safe alternative mode of GSH delivery in the peripheral blood.
RESUMEN
Several reports have suggested that ageing negatively affects the human body resulting in the alteration of various parameters important for sufficient immune health. Although, the breakdown of innate and adaptive immunity has been hypothesized to increase an individual's susceptibility to infections including Mycobacteria tuberculosis (M. tb), little research has been done to bridge this gap and understand the pathophysiology underlying how ageing increases the pathogenesis of M. tb infection. Our objective was to study research from a plethora of resources to better understand the pathogenesis of ageing and its link to the human immune system. To achieve this goal, this article explores how ageing decreases the collective T-cell immune response, reduces glutathione (GSH) production, over activates the mammalian target of rapamycin (mTORC1) pathway, inhibits autophagy and mitophagy, and alters various protective genes/transcription factors. Specifically highlighting how each of these pathways cripple an individual's immune system and increases their susceptibility from M. tb infection. Furthermore, research summarized in this article gives rise to an additional mechanism of susceptibility to M. tb infection which includes a potential defect in antigen presenting by dendritic cells rather than the T-cells response. Inflammaging has also been shown to play a role in the ageing of the immune system and can also potentially be a driving factor for increased susceptibility to M. tb infection in the elderly. In addition, this article features possible preventative strategies that could decrease infections like M. tb in this population. These strategies would need to be further explored and range from immunomodulators, like Everolimus to antioxidant supplementation through GSH intake. We have also proposed the need to research these therapies in conjunction with the administration of the BCG vaccine, especially in endemic populations, to better understand the risk contracting M. tb infection as well as ways to prevent infection in the first place.
