Study Shows Short-term Inhibition of IL-6R-HIF1α Signaling Key in Cytokine Storm Management

Researchers from  Osaka University have just discovered a new therapeutic strategy against the dreaded cytokine storms, a severe inflammatory syndrome triggered by trauma, infections, or severe burns.

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What is a cytokine storm?

Cytokines are chemical messengers that help the body eliminate invading bacteria and viruses and control inflammation. The body maintains a balance of cytokines because they help to keep the immune system healthy. However, this balance is disrupted when the immune system overreacts. A severe infection such as in the case of COVID-19 or a severe burn can trigger a cytokine storm in the body.

Read Also: Most Severe Forms of COVID-19 Are Due to Immune Suppression Not to Cytokine Storms

Many diseases can trigger a cytokine storm: These include sepsis and acute respiratory distress syndrome, viral infections, serious burns, and ischemia. People with traumatic injuries and those undergoing cancer immunotherapy can also experience this acute inflammatory event.

During this storm, also known as cytokine release syndrome (CRS), the body produces too many cytokines, leading to potentially fatal inflammation.

This extreme and excessive immune response, which often occurs in very severe forms of COVID-19, may have found a targeted treatment. The study, published in the Proceedings of the American Academy of Sciences (PNAS), shows that administering this anti-IL-6 antibody to patients suffering from sepsis, severe infections, and burns can suppress vascular damage or secondary infections.

Block IL-6, but not for too long

Interleukin-6 (IL-6) is a key cytokine in the storm because it helps trigger the inflammation that damages the body. IL-6 sends its message by binding to IL-6 receptors in the cells, which tell the cells to spread the inflammation. Because Interleukin-6 plays an important role in cytokine release syndrome, treatments that block IL-6 signaling can relieve inflammation. However, if this blockade lasts too long, there is a risk of side effects.

Read Also: Sepsis Breakthrough: A Blood Test That Can Detect the Deadly Condition in 45 Minutes

The study identified a way to block IL-6 signaling while minimizing the side effects of the treatment. The discovered antibody only blocks the IL-6 receptor for a short period. However, this short period is sufficient to protect the tissue from damage caused by cytokine storms triggered by sepsis or severe burns.

Blocking IL-6R-HIF1α signaling strengthens vascular endothelial cells

Vascular damage occurs when an infection or burn causes the cells lining the inner surface of blood vessels to leak. The leaking fluid triggers a storm of cytokines and can lead to a secondary infection. Here the mechanism is decoded: When IL-6 binds to its receptor, it activates a protein called hypoxia-inducible factor 1α (HIF1α), which increases inflammation. “We found that blocking IL-6R-HIF1α signaling strengthens vascular endothelial cells and improves vascular integrity. This prevents the vessels from leaking and relieves inflammation.”

Final thoughts

The study from Osaka University represents a significant step in treating cytokine storms. By focusing on short-term inhibition of IL-6 receptor signaling, it offers a promising and potentially safer approach to managing severe inflammation in various medical conditions. This advancement could pave the way for more effective treatments in the future.

Read Also: New Drug Shows Promise for Preventing Organ Failure Due to Sepsis

References

Kang, S., Onishi, S., Ling, Z., +9, & Kishimoto, T. (2024). Gp130–HIF1α axis–induced vascular damage is prevented by the short-term inhibition of IL-6 receptor signaling. Proceedings of the National Academy of Sciences, 121(2), e2315898120. https://doi.org/10.1073/pnas.2315898120

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