Flu's Misery May Lie in the Genes
Certain DNA could spur worse symptoms, mouse study shows
FRIDAY, Nov. 3, 2006 (HealthDay News) -- If the flu hits you especially hard this season, blame it on your DNA.
A new study of flu-infected mice found that certain genes spurred a strong immune response in the lungs that led to much more severe illness. Mice that didn't exhibit such an immune response were more likely to recover, the researchers found.
The findings may help humans not only survive the annual flu season but also an avian flu pandemic, should it ever arise.
"The long-term implications would fit into the idea of genetically based preventive medicine," explained co-researcher Dr. Linda Toth, associate dean of research at Southern Illinois University School of Medicine in Springfield. "To know that some people are predisposed to any kind of disease, we would be able to better advise or monitor those people so as to limit their health risk."
This knowledge might also help public health officials allocate precious resources.
"In the case of influenza, viral treatments and vaccine are in limited availability and if we had this kind of information, it could potentially be used to target the resources to those most at risk," Toth said.
She and co-researcher Rita Trammell, an assistant professor of internal medicine at Southern Illinois University School of Medicine, were expected to present the findings Friday at a meeting of the American Physiological Society, in Fort Lauderdale, Fla.
Another expert said the research has implications for the treatment of flu.
"It brings up the question of whether anti-inflammatories have a role in treating a flu with a lot of inflammation," said Dr. Marc Siegel, author of Bird Flu: Everything You Need to Know About the Next Pandemic and clinical associate professor of medicine at New York University School of Medicine in New York City. "It also brings up the question of 'Does genetics allow you to anticipate which group is going to have a more deleterious inflammatory response?' That would be very helpful epidemiologically."
The question of who dies of influenza has been a hot topic since at least the 1918 pandemic, which killed millions of people around the world. At the time, doctors noted that the immune systems of young, robust adults often "overreacted," resulting in a severe and often deadly inflammation of the lungs.
"This has been a long-time concern of scientists since 1918, when the theory was that people drowned in their own secretions," Siegel explained. "The body sees influenza and responds with a strong immunological response, and that response can lead to a lot of secretions."
The 1918 pandemic and the current avian flu -- which has so far killed only a small number of humans -- have some similarities: Both cause an intense inflammatory and immune response in the lungs of mice and people.
"With the current avian influenza as well as the influenza from the 1918 pandemic, the influenza caused a really enhanced and intense inflammatory and immune response in the lungs which killed the mice," Trammell said. "This was really important in determining why they died. We wanted to look at the background genetics of mice, how they reacted differently."
In their research, Trammell and Toth infected two strains of laboratory mice -- called Types "B" and "C" -- with an influenza A virus. Past work had shown that about half of the Type B mice would die, compared to about 10 percent of the Type C mice.
When lung tissue from the mice was examined about 30 hours after infection, the authors found that levels of all the pro-inflammatory cytokines (with one exception) were elevated and were much higher in the sensitive mice. This indicates a more severe inflammatory response, the researchers said. Cytokines are proteins that can cause inflammation when an immune response is mounted.
Despite the variation in inflammation, the level of the virus in the rodents' lungs was about the same in both groups.
A second, related study found that levels of immune-related messenger RNA (mRNA) in Type B mice were on average 24 times higher (and sometimes 100 times higher) than in uninfected mice. The mRNA levels in Type C mice increased less than three-fold after infection.
The next step?
"We want to try to identify specific genes or the array of genes that contribute to either the resistance or the severe response to the virus," Toth said. "Right now, we have some ideas, but we haven't nailed that down definitively."
Trammell said that this type of information, "would have enormous implications for understanding and avoiding the fatality associated with influenza virus."
For more on avian influenza, visit the World Health Organization.