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Canadian Scientists Explain How Cytokine Storms Affect Pandemic Flu Severity

Canadian scientists have helped make a discovery that might explain why some people develop severe illness when infected with H1N1 flu and others don't.

The researchers from Toronto's University Health Network found high levels of a molecule called interleukin 17 in the blood of severely ill H1N1 patients, and low levels in patients with mild forms of the disease.

Interleukin 17 is a cytokine, a kind of molecule that helps regulate the body's white blood cells which fight viral, bacterial and other infections.

But interleukin 17 can also go "out of control" in some cases and has been linked with such inflammatory autoimmune diseases as rheumatoid arthritis and asthma.

In the cases of respiratory infections, cytokines plays a part in a potentially fatal immune reaction called a "cytokine storm," in which the immune system of a healthy person goes haywire and "overreacts" to an infection. The cytokines command a patient's body to flood the lungs with fluids and mucous, which can eventually block off the airways and "drown" the patient.

Cytokine storms are what are thought to have caused many of the deaths in the SARS outbreak, bird flu, and the 1918 Spanish flu, which killed a disproportionate number of otherwise healthy adults.

For this latest study, to be published in the journal Critical Care, the Toronto researchers joined a team from Spain to examine a group of otherwise healthy Spanish patients who became infected with H1N1 during the first wave, in July and August 2009. The group included 20 hospitalized patients, 15 outpatients with mild forms of the illness, and 15 control subjects who weren't infected.

The researchers focused on 29 cytokines and analyzsed them to find any patterns among the study volunteers.

They found that those with severe symptoms from the flu had elevated levels of interleukin 17, while patients with the mild form of the disease had low levels.

Dr. David Kelvin, the leader of the Canadian team and the head of the Experimental Therapeutics Division at the Toronto General Hospital Research Institute, says the discovery is the first clue about what could be causing some patients to develop potentially fatal lung inflammation and pneumonia.

Kelvin said it is still not known whether high levels of interleukin 17 are always present in patients, or if they are overproduced only in response to the virus. But he told the Globe and Mail that IL-17 levels are likely high in patients who develop other lung infections.

"It's probably not an isolated example that is specific for H1N1, and it probably spills over to other types of respiratory illness," he said.

Kelvin said his team believes the discovery could lead to preventive therapies that would target IL-17 in future flu pandemics and other outbreaks, potentially speeding recovery.

As well, a test to determine who has high levels of the molecule could be possible in the near future.

"A diagnostic test could let us know early who is at risk for the severe form of this illness quickly," he said, noting that high levels would indicate a failure of the immune system to eliminate the virus.

He cautioned, though, that the clinical application of this work is still many years away.

Researchers are now expanding on the study to look for similar patterns in people living in other countries, such as China.

Reference Source:
December 17, 2009

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