Victims of the 1918 influenza housed in Camp Funston, KansasWIKIMEDIA COMMONS, US ARMY PHOTOGRAPHER

Researchers have identified a receptor that can block the flooding of immune cells into infected tissue that causes deadly bouts of the flu. The findings, published today (September 15) in Cell, could one day be used to develop treatments for people who are vulnerable to getting very sick from the flu.

“This was a hugely complex and very complete study,” said Herbert “Skip” Virgin, a viral immunologist at Washington University Medical School in St. Louis, who was not involved in the study.  What’s exciting is that “there’s a specific pharmacologic inhibitor molecule that can be targeted to improve clinical outcome in influenza.” The new approach is unique, he added, because it targets the reaction of the host, rather than characteristics of the virus, which can easily evolve to evade most therapies.

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Michael Oldstone, an experimental biologist at the Scripps Research Institute in La Jolla, California, was trying to untangle the pathways that led to cytokine storms in influenza, while his colleague Hugh Rosen, a chemical biologist at the same institution, was studying a receptor called sphingosine-1-phosphate (S1P1) known to modulate immune cell trafficking. Putting their research together, they found the answer Oldstone had been looking for.

The group created mice that expressed fluorescent versions of the S1P1 receptor and pinpointed them to endothelial cells that line blood vessels in the lungs. Administering a molecule that binds the S1P1 receptor quieted cytokine storms in mice, but did not affect the immune system’s ability to fight the infection. Finally, they infected mice with the swine flu and showed that binding the S1P1 receptor muted the cytokine response and reduced mortality. The approach could “differentially affect the collateral damage caused by the immune system while still allowing the host to eradicate the virus,” Rosen said.

The findings suggest that people could one day be treated with an S1P1 agonist and an anti-viral agent to blunt the severity of the flu, Oldstone added.

The new research could also help discover genetic markers that may predict who will fare worst with the flu. “One of the things we need to focus on going forward is defining precisely, in genetic terms, people who are susceptible to cytokine storms,” Rosen said.

J. Teijaro, et. al, “Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection”Cell, doi:10.1016/j.cell.2011.08.015, 2011

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