New Study Find That IL-1 Beta as a Key Driver of COVID-19 Severity and Not Inflammasome Activation and Pyroptosis!
Nikhil Prasad Fact checked by:Thailand Medical News Team Feb 28, 2025 6 hours, 26 minutes ago
Medical News: Researchers from the Walter and Eliza Hall Institute of Medical Research in Australia have uncovered new insights into how severe COVID-19 develops in some patients. Their findings indicate that a protein called interleukin-1 beta (IL-1β) plays a major role in driving the disease's severity. Interestingly, they found that this process happens independently of certain well-known inflammation pathways. This
Medical News report explores their key discoveries and what they mean for future treatments.
New Study Find That IL-1 Beta as a Key Driver of COVID-19 Severity and Not Inflammasome Activation and Pyroptosis
Severe cases of COVID-19 are often linked to an excessive immune response known as a "cytokine storm." In this response, the immune system releases high levels of inflammatory proteins, which can cause damage to the lungs and other organs. Scientists have long suspected that specific types of programmed cell death, particularly pyroptosis, contribute to this excessive inflammation. Pyroptosis is a form of cell death triggered by inflammasomes, which are protein complexes inside immune cells that help fight infections. However, the latest study challenges this view and suggests that IL-1β contributes to severe disease through a different mechanism.
The Study and Its Key Findings
To investigate how IL-1β affects COVID-19 severity, researchers conducted experiments on genetically modified mice infected with a mouse-adapted SARS-CoV-2 virus. The study focused on mice that lacked specific genes involved in the inflammasome and pyroptosis pathways. These included genes for key proteins like NLRP1, NLRP3, ASC (an inflammasome adapter protein), and gasdermin D (GSDMD), which is essential for pyroptosis. The surprising result was that even when these pathways were disabled, IL-1β levels remained high, and the disease severity did not significantly change.
One of the most important findings was that mice completely lacking IL-1β had much better survival rates compared to normal mice infected with SARS-CoV-2. These IL-1β-deficient mice also experienced less weight loss, which is a key measure of disease severity in animal studies. Interestingly, removing another inflammatory protein, IL-18, did not have the same protective effect. This suggests that IL-1β, rather than IL-18, is the main driver of severe COVID-19-related inflammation.
IL-1β and Age-Related COVID-19 Severity
Older adults have a much higher risk of severe COVID-19 compared to younger individuals. To explore whether IL-1β plays a role in this increased vulnerability, researchers compared young and old mice with and without the IL-1β gene. The results showed that IL-1β deficiency significantly reduced disease severity in both age groups, but older mice still experienced worse outcomes overall. This suggests that while IL-1β is a key contributor to severe COVID-19, other age-related factors also play a role.
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;strong>Testing Potential Treatments
Given that IL-1β plays such a crucial role in severe COVID-19, the researchers tested whether blocking IL-1β with a drug could improve outcomes. They used anakinra, a medication that blocks IL-1 signaling and is already used to treat inflammatory conditions like rheumatoid arthritis. Surprisingly, despite the genetic evidence showing that IL-1β deficiency reduces disease severity, anakinra treatment did not provide significant protection in their mouse model. This raises questions about whether current IL-1-targeting treatments are effective enough to counteract severe COVID-19 inflammation.
Implications and Future Research
The findings from this study provide new insights into how severe COVID-19 develops and challenge previous assumptions about the role of pyroptosis and inflammasomes. They also highlight IL-1β as a major target for future treatments. However, the fact that anakinra did not significantly improve survival in mice suggests that better ways to block IL-1β might be needed.
For researchers and clinicians, these results emphasize the need to explore new strategies for controlling IL-1β-driven inflammation. Potential approaches could include developing more effective IL-1β inhibitors or finding other molecules involved in its activation. Additionally, combining IL-1β-targeting treatments with other anti-inflammatory strategies may offer better results.
Conclusion
This study offers a breakthrough in understanding why some people develop severe COVID-19 while others experience mild illness. By showing that IL-1β plays a crucial role in driving severe disease, but does so independently of previously suspected pathways, the research opens up new directions for treatment. The fact that blocking IL-1β genetically was more effective than using an existing drug suggests that stronger or more targeted therapies may be needed. While more studies are required to fully translate these findings into clinical practice, the research represents an important step toward better treatments for severe COVID-19.
The study findings were published in the peer-reviewed journal: Cell Death & Differentiation.
https://link.springer.com/article/10.1038/s41418-025-01459-x
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