Flu Infections Can Cause Deadly Cytokine Storm That Sparks Lung Inflammation

Intravenous Needle in HandInfection with the flu (influenza) can lead to a dangerous and deadly conditional known as a cytokine storm. Now researchers at The Scripps Research Institute (TSRI) have mapped key elements of the severe immune overreaction that can cause severe sickness and even death in patients infected with certain strains of the flu virus.

Also known as a cytokine cascade or hypercytokinemia, a cytokine storm causes highly elevated levels of various cytokines as a result of a positive feedback loop between cytokines and immune cells. Cytokines are small proteins important in cell signaling that modulate the balance between humoral and cell-based immune responses.

Cytokine storms are especially dangerous in regards to the flu because the overreaction can cause lung inflammation and fluid buildup that can lead to respiratory distress as well as a secondary bacterial pneumonia. Symptoms of a cytokine storm include high fever, swelling and redness, extreme fatigue, and nausea. The severe immune overreaction can be fatal in some individuals.

Researchers believe that cytokine storms are a likely major cause of the high mortality rates during the “Spanish flu” of 1918 to 1920 that killed more than 50 million people worldwide as well as the more recent H1N1 “swine flu” and H5N1 “bird flu” outbreaks.

Now researchers in the present study have identified endothelial cells lining blood vessels in the lungs as the central orchestrators of the cytokine storm and immune cell infiltration during H1N1 flu infection. The findings may aid in the development of a potent new class of anti-inflammatory compounds that prevent this immune overreaction in animal models.

States first author John R. Teijaro, an assistant professor in TSRI’s Department of Immunology and Microbial Science, “We show that with this type of drug, we can quiet the storm enough to interfere with the virus-induced disease and lung injury, while still allowing the infected host to mount a sufficient immune response to eliminate the virus.”

Adds senior author Hugh Rosen, professor in TSRI’s Department of Chemical Physiology, “This study provides insights into mechanisms that are chemically tractable and can modulate these cytokine storms.”

In a separate study, the researchers discovered that using a candidate drug compound to activate immune-damping receptors (S1P1 receptors) on the same endothelial cells could calm a cytokine storm in mice and ferrets. Quieting the storm lowered death rates from the flu in the animals.

States Teijaro, “That was really the first demonstration that inhibiting the cytokine storm is protective.”

The findings of the present study may help develop drugs that can lower the death rate associate with the flu. At the present, the only means of protection against the flu is the flu shot, or influenza vaccine.


Flu infections can lead to deadly cytokine storm that sparks lung inflammation:
Scripps Research Institute Scientists Describe Deadly Immune ‘Storm’ Caused by Emergent Flu Infections:

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