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Selective Impact of Selenium Compounds on Two Cytokine Storm Players
Indu Sinha1, Junjia Zhu2, Raghu Sinha1
1Department of Biochemistry and Molecular Biology, Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA 17033, USA.
Insights
Selenium compounds, particularly methylseleninic acid (MSeA), can reduce key cytokine storm players like IL-6 and TNF-α. This suggests MSeA could be a beneficial addition to COVID-19 treatment strategies.
Area of Science:
- Immunology
- Pharmacology
- Molecular Biology
Background:
- Cytokine storm is a severe complication in COVID-19, leading to organ damage.
- Current treatments for cytokine storm have limited success.
- Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) are key mediators of cytokine storm.
Purpose of the Study:
- To evaluate the potential of selenium compounds to mitigate cytokine storm in vitro.
- To investigate the efficacy of methylseleninic acid (MSeA) in reducing IL-6 and TNF-α secretion.
- To explore the molecular mechanisms of MSeA, including its effect on Nrf2 and IκBα pathways.
Main Methods:
- In vitro evaluation of four selenium compounds using THP-1 macrophages.
- Lipopolysaccharide (LPS) challenge to induce cytokine production.
- Measurement of IL-6 and TNF-α levels.
- Analysis of Nrf2 and IκBα protein levels following MSeA treatment.
Main Results:
- Methylseleninic acid (MSeA) demonstrated the most significant reduction in IL-6 and TNF-α secretion among the tested selenium compounds.
- MSeA treatment led to increased Nrf2 activation and decreased phosphorylated IκBα (pIκBα) in human macrophages.
- These findings highlight MSeA's potent anti-inflammatory effects.
Conclusions:
- Selenium, specifically MSeA, shows promise in suppressing key mediators of the cytokine storm.
- MSeA may offer a therapeutic benefit for COVID-19 patients by reducing detrimental inflammatory responses.
- Further clinical investigation into MSeA as an adjunct therapy for COVID-19 is warranted.
Abstract:
COVID-19 patients suffer from the detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium to reduce the impact of two important cytokine storm players: IL-6 and TNF-α. The effects of four selenium compounds on the secretion of these cytokines from THP-1 macrophages were evaluated in vitro following an LPS challenge. Also, the potential impact of methylseleninic acid (MSeA) on Nrf2 and IκBα was determined after a short treatment of THP-1 macrophages. MSeA was found to be the most potent selenium form among the four selenium compounds tested that reduced the levels of IL-6 and TNF-α secreted by THP-1 macrophages. In addition, an increase in Nrf2 and decrease in pIκBα in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit from the addition of MSeA to the standard therapy due to its ability to suppress the key players in the cytokine storm.
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