HEALTH: Scripps research finds key to flu's deadly nature
Based on studies in mice, researchers led by Scripps scientists Hugh Rosen and Michael Oldstone say the cause lies in the lining of certain blood vessels in the lungs. These cells trigger release of infection-fighting chemicals called cytokines. In some people, their production gets out of control, causing what's called a " cytokine storm ." This can cause production of excess fluid that fills tiny air sacs in the lungs and harms other organs.
Moreover, their proposed technique to treat flu doesn't involve attacking the flu viruses, and therefore shouldn't be vulnerable to development of viral resistance. And the researchers say a test could possibly be developed to identify those at highest risk of dying from the flu.
Cytokine storms are believed to have helped cause the massive death toll of the 1918-19 flu pandemic and the smaller number of deaths in the more recent swine and avian flu outbreaks. However, their source wasn't known until this study , which was published online Thursday in the journal Cell.
Surprisingly, the triggering cells are not themselves infected by the flu virus .
The study found that the cytokine storm can be reduced with drugs that target a surface molecule on the cells called the S1P1 receptor, which serves as a gateway into the cell. In mice, these receptor-targeting drugs reduced the response and increased survival rates for mice exposed to the H1N1 virus, which caused a pandemic in 2009.
Other microbes also trigger cytokine storms, Rosen said, including hantavirus and HIV and a bacterial form of pneumonia. It's also involved in some autoimmune diseases such as multiple sclerosis. Drugs targeting the S1P1 receptor are already in human trials for autoimmune diseases.
"This research opens up an additional usage for S1P1 receptor modulators, and additional work is now needed to define what the best properties for an S1P1 modulator would be for this particular use," Rosen said. Such a drug could be given in combination with an antiviral flu drug such as Tamiflu, he said.
Rosen and Oldfield discussed their research in a video available on YouTube .
In a human treatment, the goal would be to reduce the overactivity of cytokines, but not to eliminate them entirely, the researchers said in a Wednesday interview. The cytokines play an important role in helping the body resist infection, they said.
It's likely that cytokine overactivity is caused by "maladaptions" in the genetic composition of patients that make them overreact to viral infections, Rosen said.
"One of the goals now of our program is to really understand where these markers may be at the genetic and biochemical levels that allow us to predict these maladaptions in human populations," Rosen said.
The research was funded by grants from the U.S. Public Health Service; the National Institute of Allergy and Infectious Diseases ; and the NIH Common Fund .