The administration of GA/18β treatments prevents the elevation of IL-17A and IL-2 interleukins
inflammation, TNF-α, infection
SARS-COV-2 INFECTION, INFLAMMATION, DISEASE, INFECTION, PATHOGENESIS
The modulation of cytokines, particularly IL-17A and IL-2, was observed in response to GA/18β treatments for SARS-CoV-2 infection. Emerging evidence underscores the vital role of IL-17 in COVID-19 pathogenesis, with its capacity to activate various pro-inflammatory cytokines like IL-6, IL-1β, IL-1, and IL-8 (In our study, we observed a substantial induction of IL-17A in the control group of COVID-19 patients up to day 8, after which the IL-17A concentration remained significantly elevated compared to the GA/18β treated groups (Due to the known capacity of IL-17A to activate various cytokines and the positive correlation found between IL-17A and IL-6, IL-8, and TNF-α, the increase in IL-17A could potentially trigger dysregulated pro-inflammatory responses. This, in turn, may lead to elevated levels of the inflammatory cytokines IL-6, IL-8, and TNF-α in patients in the control group. Considering the reported role of TNF-α in stimulating inflammatory cytokines, it is suggested that the observed increase in TNF-α over time in non-GA/18β treated patients could also contribute to the significant increase in IL-6 and IL-8 release. While the observed increase in IL-1β in the control group was not statistically significant, it is probable that TNF-α and IL-17A could influence the increase in this cytokine. For example, in fibroblast cells, the interaction between IL-17 and low proportions of TNF-α has been observed to result in a synergistic pro-inflammatory effect, stimulating high concentrations of IL-6, IL-8, and IL-1β (Conversely, in the GA/18β treated groups, we observed the attenuation of IL-6, IL-8, and IL-1β, likely resulting from the lower stimulation of IL-17A and TNF-α. This, in turn, could mitigate further pro-inflammatory stages (Reduction of IL-17 levels by dose B in SARS-CoV-2 infected subjects could probably result from two different pathways: inhibition of the HMGB1-mediated inflammation response, as GA and 18β can directly bind to HMGB1 (Another interleukin significantly influenced by the treatments was the proinflammatory cytokine IL-2, which participates in T-cell activation and the production of cytokines TNF-α and IFN-γ (Despite the overall reduction in IL-2 levels due to GA/18β treatments, it was observed that dose B induced IL-2, compared to dose A, in the initial 3 days of infection, a period when disease symptoms are most pronounced. Importantly, this IL-2 induction did not persist after day 3, possibly allowing for heightened IFN-γ production during the early stages of infection in the dose B-treated group (