Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 08, 2024 3 hours, 18 minutes ago
Medical News: As scientists continue to explore ways to manage COVID-19, one area of interest is how the immune system's response could be modulated to prevent severe symptoms. Researchers from Spain's Instituto de Investigaciones Biomédicas Sols-Morreale, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), and Universitat de Barcelona have recently focused on nitric oxide (NO), a compound known to influence immune function, and its impact on macrophages, a type of immune cell heavily involved in fighting infections.
How Nitric Oxide Could Help Macrophages Fight COVID-19’s Cytokine Storm
The cytokine storm - an excessive immune response characterized by the release of large amounts of inflammatory molecules - is a dangerous feature of severe COVID-19. This
Medical News report examines how nitric oxide affects human macrophages challenged by the cytokine storm, aiming to clarify its potential as a supportive treatment.
What is Nitric Oxide’s Role in Immunity?
Nitric oxide, a small molecule produced in the body, is known for its anti-inflammatory and antimicrobial properties. However, unlike animal models that readily produce nitric oxide through the enzyme NOS2, human macrophages often struggle to generate sufficient nitric oxide under inflammatory stress. To mimic nitric oxide production in humans, researchers introduced an NO donor to macrophages exposed to a simulated cytokine storm, testing if it could improve the cells' response.
The researchers observed that nitric oxide administration influenced the macrophages' metabolic pathways, reducing some harmful effects of the cytokine storm. These effects on cellular metabolism and inflammatory markers were explored through a range of methods, including metabolic assays and transcriptomic analysis.
Nitric Oxide and Cell Health
One of the main findings from this study was that nitric oxide helped to maintain the viability of macrophages exposed to the cytokine storm. In this pro-inflammatory environment, nitric oxide limited cell death by increasing protective molecules within the cell. The study showed that nitric oxide reduced oxidative phosphorylation, the cell's primary energy-generating process, thereby increasing the use of glycolysis. This shift in energy production helped the cells withstand the inflammatory stress and continue functioning, even when exposed to the cytokine storm.
Interestingly, nitric oxide also affected the production of reactive oxygen species (ROS), which are molecules produced by immune cells to kill pathogens. Excessive ROS can damage healthy cells, but nitric oxide controlled the ROS levels in a way that enhanced their antimicrobial effect without harming the macrophages.
Impact on Metabolic Pathways
Nitric oxide also shifted the macrophages’ metabolic processes, which play a significant role in determining immune cell b
ehavior. In the presence of the cytokine storm, the researchers noted an increase in glycolysis, the process by which cells break down glucose for energy. Additionally, nitric oxide administration reduced the activity of the TCA cycle (a core part of cellular respiration) and mitochondrial respiration. This shift to glycolysis allowed the macrophages to maintain energy levels without overtaxing their mitochondria, the cell’s energy powerhouse.
Another critical effect was the reduction of itaconate, a metabolite that often accumulates in response to the cytokine storm. Itaconate can inhibit certain enzymes essential for mitochondrial function, contributing to cell dysfunction. Nitric oxide treatment helped to balance itaconate levels, potentially restoring more normal cellular function in the presence of the cytokine storm.
Gene Expression and Immune Response
To delve deeper into the effects of nitric oxide, researchers examined gene expression in the treated macrophages. The presence of nitric oxide altered several key genes linked to inflammation, including those involved in the NF-κB pathway, a signaling pathway essential in immune responses. In response to nitric oxide, macrophages displayed reduced expression of genes tied to pro-inflammatory pathways. At the same time, nitric oxide enhanced the expression of genes that contribute to anti-inflammatory responses, suggesting a dual benefit of controlling excessive inflammation while maintaining an effective immune response.
Future Implications and Clinical Relevance
The findings offer a promising outlook for nitric oxide as an adjunct treatment in managing severe COVID-19. By protecting macrophages from cell death and modulating inflammatory responses, nitric oxide may help the immune system fight COVID-19 more effectively, reducing the risk of complications associated with an overactive immune response.
The study encourages further investigation into nitric oxide therapy for COVID-19 patients, with the hope that it could be a viable option for those experiencing severe symptoms. Additional research and clinical trials are necessary to confirm these benefits and determine the best delivery methods and dosages of nitric oxide in human patients.
Conclusion
In summary, nitric oxide’s impact on macrophages offers an innovative approach to treating severe COVID-19. By supporting cell viability, modulating metabolism, and balancing inflammation, nitric oxide shows potential to ease the effects of the cytokine storm and improve patient outcomes. The findings indicate that nitric oxide could be instrumental in mitigating the severe immune reactions seen in COVID-19, representing a new frontier in the fight against the pandemic.
The study findings were published in the peer-reviewed journal: Advanced Healthcare Materials.
https://onlinelibrary.wiley.com/doi/10.1002/adhm.202401688
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