And it wasn’t just in 1918. The 2009 swine flu killed more than 18,000 people worldwide, according to the World Health Organization. Scientists say immune overreactions caused the majority of those fatalities.
New research about how the virus works on the cellular level has uncovered what makes influenza so deadly: It destroys its host — you — by using your body’s own defenses against itself.
The research about such exaggerated immune responses could lead to more-effective flu drugs and radically change the way all kinds of infections are treated, leading virologists say.
“This is where the science [on epidemiology] is right now,” said Trish Perl, a senior epidemiologist at Johns Hopkins Hospital. “That’s what happens with a lot of severe infections. . . . It’s almost like the system goes into overdrive.”
While trying to destroy flu-infected cells, your immune system also destroys legions of perfectly healthy cells all over your body. This is why, even though the virus itself rarely ventures outside the lungs, the symptoms of the flu are so widespread, according to Michael Oldstone, a virologist at the Scripps Research Institute in La Jolla, Calif.
“If you get a cold or the flu, you get fever, pains, upset stomach,” Oldstone said. “That’s all due to the immune response.”
Most of the time, this immune response isn’t too severe. As the virus runs its course, the response subsides. But in some cases, an infection can trigger a reaction so destructive it can be fatal. Scientists call this a cytokine storm, because of the violent way immune cells respond to a virus. (A cytokine is a molecule that immune cells use to send signals between one another.) Cytokines usually help fight off infections by telling the immune system which specific viral cells it should be attacking. But sometimes an overabundance of cytokines floods into a part of the body, and that’s when you get a storm.
Cytokine storms are rare, but Perl said they may be more common among younger people because they have stronger immune systems, which are more prone to overreactions. She said this may explain one of the more surprising outcomes of the 2009 swine flu: that it was deadlier among young people than it was among the elderly.
During flu infections, Oldstone said, cytokine storms can cause serious damage throughout the body, especially in the lungs. This, he said, combined with the lung damage cause by the influenza virus itself, leads to fatal cases of pneumonia.
Oldstone and two other researchers have been looking into cytokine storms for more than five years. They’ve identified a receptor on an endothelial cell called S1P1, and found that S1P1 signaling by endothelial cells initiates the cascade of events leading to a cytokine storm. The virologists’ findings, published in a recent issue of the scientific journal Cell, could pave the way for a new class of immune-reaction-blocking drugs that could be more effective than antiviral drugs.