NIH Research Matters
August 13, 2007
Immune System "Storm" May Not Be Key to Bird Flu Deaths
Recent research has suggested that the immune system's overreaction to certain "bird flu" strains such as H5N1 may be the key to their lethal effects. By blocking the body's hyperactive immune response, scientists had hoped to provide new lifesaving treatments. A new study, however, may have them rethinking this potential approach.
Research on the bird flu's cousin, the 1918 Spanish influenza virus, suggests that this virus was so lethal because the immune system overreacted to the virus, causing a complex "cytokine storm" in the body. Cytokines are immune molecules that help coordinate immune cells to fight off infection. In small doses they are protective, but at larger doses, they can be very destructive, creating uncontrolled inflammation leading to tissue damage.
Autopsies of recent bird flu victims showed evidence of a cytokine storm and severe lung damage similar to that caused by the 1918 flu virus. Dr. Robert Webster and his colleagues at the St. Jude Children's Research Hospital tested whether blocking the cytokine storm could protect mice that were infected with avian flu virus. The study received financial support from NIH's National Institute of Allergy and Infectious Diseases (NIAID).
The researchers used mice that were genetically altered to either lack or be unable to respond to 1 of 3 different cytokines. Prior studies have shown that these cytokines increase following avian flu infection and play a role in attracting immune cells to the lung, where they cause fatal damage.
In the July 24, 2007, issue of the Proceedings of the National Academy of Sciences, the authors reported that the genetically altered mice infected with the H5N1 avian flu virus had similar mortality rates and lost about the same amount of weight as infected normal mice.
The researchers also treated infected normal mice with glucocorticoids, steroids that suppress cytokine levels. The treatment, they found, did not help the infected mice live longer than their untreated counterparts.
Although these results are in mice and not people, they cast doubt on the popular paradigm that the cytokine storm is what causes death from avian flu viruses such as H5N1. Future research is needed to further explore whether therapies targeting the virus itself, rather than the hyperactive immune response, will be a more promising strategy to control avian flu.—by Deborah Stewart, Ph.D.
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