Administration of anti-IL-6 drug with short half-life to patients with sepsis, ARD, burns, etc. should suppress vascular damage or secondary infections. Credit: Osaka University
Cytokines are chemical messengers that help the body get rid of invading bacteria and viruses and control inflammation. The body carefully balances cytokines because they help keep the immune system healthy. However, this balance is disrupted if the immune system overreacts. A serious infection or severe burn can trigger a cytokine storm in the body. During the storm, also called cytokine release syndrome (CRS), the body produces too many cytokines, leading to life-threatening inflammation.
Interleukin-6 (IL-6) is a key cytokine in the storm because it helps trigger the inflammation that damages the body. IL-6 delivers its message by attaching to IL-6 receptors in cells, which signals the cells to spread inflammation. Because IL-6 is important in CRS, treatments that block IL-6 signaling may relieve inflammation. However, this blockage tends to last a long time, leading to side effects.
In a study published in the Proceedings of the National Academy of Sciences, researchers at Osaka University have discovered a way to block IL-6 signals while minimizing treatment side effects. The group interrupted the inflammatory signal using an antibody that blocks the IL-6 receptor for only a short time. The brief interruption was long enough to protect tissues from injury from cytokine storms caused by sepsis or severe burns.
“Our results suggest that CRS can be treated with an IL-6 receptor antibody that has a short half-life,” says Sujin Kang, lead author of the study. “This can prevent vascular damage and at the same time reduce the side effects associated with IL-6 blockade.”
Vascular damage occurs when an infection or burn causes cells that line the inner surface of blood vessels to leak. The leaking fluid triggers a cytokine storm and can cause a secondary infection. The group also reported a potential mechanism for this cell damage. When IL-6 binds to its receptor, it activates a protein called hypoxia-inducible factor 1α (HIF1α), which amplifies inflammation.
“We found that blocking the IL-6R-HIF1α signal strengthened vascular endothelial cells and improved vessel integrity. This helped prevent vessel leakage and relieved inflammation caused by CRS,” explains the author. principal Tadamitsu Kishimoto. “We hope this will help patients suffering from CRS and other inflammatory diseases in the future.”
Other illnesses that can cause CRS include sepsis and acute respiratory distress syndrome, COVID-19 infection, and ischemia. People with traumatic injuries and those undergoing cancer immunotherapies may also experience a cytokine storm. We hope that the results of this study can provide an alternative therapeutic approach to patients suffering from these pathologies.
More information:
Sujin Kang et al, Vascular damage induced by the Gp130–HIF1α axis is prevented by short-term inhibition of IL-6 receptor signaling, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2315898120
Provided by Osaka University
Quote: New targeted treatment calms the cytokine storm (January 17, 2024) retrieved January 17, 2024 from
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