Oxidative Stress Mediates Cross-Talk between the Thioredoxin System and NLRP3 Inflammasome in Patients with COVID-19.

Background: COVID-19 is known as a fatal respiratory disease with an inflammatory basis. Imbalance of the thioredoxin system in peripheral blood mononuclear cells (PBMCs) may cause NLRP3 inflammasome activation and interleukin-1β production. Materials and Methods: Forty patients with COVID-19 and forty healthy individuals were included in this case-control study. All participants had previously received two doses of the coronavirus vaccine. PBMCs were isolated, and the expression of thioredoxin-interacting protein (TXNIP), thioredoxin-1 (TRX-1), NLRP3, caspase-1, and IL-1β genes was determined. Protein levels of TXNIP, NLRP3, and IL-1β were measured. Moreover, to confirm the involvement of oxidative stress in evoking inflammation in COVID-19, PBMCs were isolated from three independent healthy subjects, cultured Results: Oxidative stress was higher in COVID-19 patients. The mRNA expression and protein levels of TXNIP, NLRP3, and IL-1β were significantly higher in PBMCs of COVID-19 patients compared with the control group, whereas the expression of TRX-1 was found to be lower in patients. The enhancement in ROS, TXNIP protein, and NLRP3 gene expression levels was positively associated with increased IL-1β. Conclusion: The concurrent elevation of ROS, TXNIP, NLRP3, and IL-1β suggests the potential role of the thioredoxin system in activating the NLRP3 inflammasome and generating inflammatory IL-1β in patients with COVID-19. In addition, vitamin C, as an adjunct therapeutic agent, beneficially suppressed oxidative stress and inflammation in infected PBMCs.