Controlling lung inflammation
28 July 2008
The symptoms of influenza, such as breathlessness, weight loss and fever, are exacerbated by an exaggerated immune system response, rather than by the virus itself. The virus is often cleared from the body by the time symptoms appear and yet symptoms can last for many days because the immune system continues to fight the damaged lung.
The immune system is essential for clearing the virus, but it can damage the body when it overreacts if it is not quickly contained. Such overreaction occurs in a number of diseases as well as influenza, such as asthma and inflammatory conditions in the gut.
During influenza infection, the immune system’s prolonged response causes the lungs to become inflamed and this can clog the airways and cause difficulty breathing.
The new study, published in the journal ‘Nature Immunology’, led by researchers from Imperial College London, reveals how the activity of immune cells in the lung is normally kept under control by a receptor known as CD200R working with another molecule called CD200.
The receptor is found in high levels in the lungs and the new research shows that it is able to limit the immune system's response and turn off inflammation once it has started.
Influenza overrides the CD200 molecule and without the molecule to bind to, the receptor cannot work to prevent the immune system from overreacting, so the lungs become inflamed.
In the new study, the researchers gave mice infected with influenza an antibody to stimulate CD200R, to see if these would enable the receptor to bring the immune system under control and reduce inflammation. The mice that received treatment had less weight loss than control mice and less inflammation in their airways and lung tissue. The influenza virus was still cleared from the lungs within seven days and so this strategy did not appear to affect the immune system’s ability to fight the virus itself.
Following these results in mice, the researchers hope that a therapy can be developed for people that would work quickly with the receptor and stop the immune system from fighting when it is no longer needed. They believe this would quickly reduce symptoms and reduce the damage that the immune system causes in the lungs and elsewhere.
Dr Robert Snelgrove, a Sir Henry Wellcome Postdoctoral Fellow at Imperial College London, one of the authors of the paper, said: “Although flu is just an inconvenience for some people, it can be dangerous and even fatal in the very young and elderly. We hope our research could ultimately help to develop treatments which fight the effects of this sometimes lethal virus.”
The researchers hope that in the event of a flu pandemic, such as a pandemic of H5N1 avian flu that had mutated to be transmissible between humans, the new treatment would add to the current arsenal of antiviral medications and vaccines. One key advantage of this type of therapy is that it would be effective even if the flu virus mutated, because it targets the body’s overreaction to the virus rather than the virus itself.
In addition to the possible applications for treating influenza, the researchers also hope their findings could lead to new treatments for other conditions where excessive immunity can be a problem, including other infectious diseases, autoimmune diseases and allergy.
The research was funded by the Medical Research Council, the US National Institutes of Health, the Wellcome Trust and the European Union.
The 2008 Sir Henry Wellcome Postdoctoral Fellowships will be announced in August.
Image: Diagram of lungs; Miles Kelly Art Library/Wellcome Images