cellular regulators of cytokine storms identified

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Blocking Flu Death

Researchers have identified the cellular regulators of cytokine storms in

influenza, which cause serious illness and death.

By Tia Ghose | September 15, 2011

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.

When a person gets the flu, the body sends immune signaling molecules called

cytokines to kill the infection. Normally, cytokines direct immune cells to

infiltrate infected tissue, such as lung tissue, and cause a few days of cough,

fever, and achy joints. But occasionally, the body whips up a cytokine storm and

a massive amount of the immune molecules flood the system, causing inflammation

and sometimes severe illness and death. Cytokine storms are thought to have

played a role in the unusually high mortality rate amongst the young and healthy

in the Spanish Influenza of 1918, as well as the higher death rate seen in swine

flu.

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

http://the-scientist.com/2011/09/15/blocking-flu-death/

http://www.msnbc.msn.com/id/44538446/ns/health-cold_and_flu/#