β-D-mannuronic Acid (M2000) and Inflammatory Cytokines in COVID-19; An In vitro Study

Area of Science:

• Immunology
• Pharmacology
• Virology

Background:

• Coronavirus disease 2019 (COVID-19) can lead to severe complications like acute respiratory distress syndrome (ARDS), cytokine storm, and multiorgan failure.
• Anti-inflammatory agents including corticosteroids, monoclonal antibodies, and NSAIDs are used to manage these complications.
• Identifying novel therapeutic agents to modulate the inflammatory response in COVID-19 is crucial.

Purpose of the Study:

• To evaluate the immunomodulatory effects of mannuronic acid (M2000), a novel NSAID, on cytokine storms in patients with COVID-19 and ARDS.
• To investigate M2000's impact on inflammatory gene expression and cytokine levels in vitro.

Main Methods:

• The study utilized blood samples from 30 COVID-19 patients with ARDS.
• Peripheral blood mononuclear cells (PBMCs) were isolated and treated with M2000 at 25 µg/well and 50 µg/well.
• Quantitative real-time PCR (qRT-PCR) assessed mRNA gene expression, and ELISA measured cytokine levels (IL-6, IL-17, TNF-α, IFN-γ).

Main Results:

• M2000 treatment significantly decreased mRNA expression of IL-17, TNF-α, IL-6, and IFN-γ in PBMCs.
• Supernatant levels of these key inflammatory cytokines were also reduced in M2000-treated groups compared to controls.
• These findings demonstrate M2000's ability to suppress key inflammatory mediators in an in vitro model.

Conclusions:

• Mannuronic acid (M2000) exhibits significant immunomodulatory effects by reducing inflammatory cytokine production and gene expression in COVID-19 patient-derived PBMCs.
• This in vitro study provides the first evidence of M2000's potential efficacy in mitigating the inflammatory cascade associated with severe COVID-19.
• Further in vitro and in vivo studies are warranted to establish M2000 as a potential novel NSAID therapeutic for COVID-19 patients.