Some fascinating research coming out of The Scripps Research Institute today that looks at what may turn out to be a new way of treating serious illness due to influenza.
Rather than trying to combat the virus – which has a nasty habit of evolving resistance to antivirals - they are looking at ways of reducing the body’s sometimes excessive immune response known as a Cytokine Storm.
Right now their research has been conducted on mice, and it is helping to unlock the long standing mystery of how and where cytokines are produced.
Cytokines are a category of signaling molecules that are used extensively in cellular communication. They are often released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.
This cascade of immune cells rushing to the infection, if it races out of control, can literally kill the patient. Their lungs can fill with fluid (which makes a terrific medium for a bacterial co-infection), and cells in the lungs (Type 1 & Type II Pneumocytes) can sustain severe damage.
Previously, in Swine Flu Sequelae and Cytokine Storm Warnings, we looked at some of the severe lung damage during the 2009 pandemic that was thought to be due to this overreaction of the immune system.
All of which serves as prelude to a study published today in the Journal Cell with the somewhat daunting title of:
Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection
Cell, Volume 146, Issue 6, 980-991, 16 September 2011 10.1016/j.cell.2011.08.015
John R. Teijaro, Kevin B. Walsh, Stuart Cahalan, Daniel M. Fremgen, Edward Roberts, Fiona Scott, Esther Martinborough, Robert Peach, Michael B.A. Oldstone, Hugh Rosen
We have two explanations available to us, one pretty basic, and a second with more meat to it.
First, the basics from a Cell Press Release.
Most of the time, being ill with the flu is little more than a nuisance. Other times, it can spark an exaggerated immune response and turn deadly. Researchers reporting in the September 16th issue of the journal Cell, a Cell Press publication, have now traced the origins of this severe immune response -- called a cytokine storm -- to its source.
Cytokines are the chemical signals that drive inflammation, and cytokine storms are thought to be the cause of many of the deaths attributed to the 1918 worldwide influenza pandemic and to the more recent outbreaks of swine and bird flu infection. The new study provides encouraging news by offering the foundations for a completely new kind of flu therapy.
"We are showing for the first time that you can actually separate the deleterious events from those needed to control the virus," said Hugh Rosen, senior author of this study, from The Scripps Research Institute.
"It had been thought for a long time that all injury from influenza was due to the virus itself, consequently, and rationally, the focus was on developing antiviral drugs," said study co-author Michael Oldstone, also of Scripps.
The new results suggest that drugs aimed at the dangerous immune response may offer a life-saving new line of defense, by protecting infected hosts from themselves. Another bonus is that such an approach doesn't put the same pressure on viruses to adapt and develop drug resistance.
The cytokines associated with flu infection were thought to come from virus-infected cells found primarily in the lungs and nasal passages. The authors find that the cytokines are instead released from the endothelial cells that line blood vessels. A protein found on the surface of endothelial cells, called Sphingosine-1-phosphate receptor (S1P1), is essential for flu-associated cytokine storms.
In mice treated with a molecule that targets S1P1, cytokine production and the early signs of inflammation are suppressed. As a result, the animals are much more likely to survive infection with H1N1 swine flu virus. Notably, several companies are already testing S1P1-targeted drugs in clinical trials, the researchers say.
A more in-depth explanation can be found in The Scripps Research Institute’s press room.
LA JOLLA, CA – September 15, 2011 – Researchers at The Scripps Research Institute have found a novel mechanism by which certain viruses such as influenza trigger a type of immune reaction that can severely sicken or kill those infected.
This severe immune reaction—called a “cytokine storm”—floods the tiny air sacs of the lungs with fluid and infection-fighting cells, blocking off airways and damaging body tissues and organs. Cytokine storms are believed to have played a major role in the staggering mortality of the 1918-1919 worldwide influenza pandemic, as well as in the more recent swine flu and bird flu outbreaks.
And lastly, in concert with the publication of this study, two of the primary researchers - Professors Michael BA Oldstone and Hugh Rosen – discuss their findings in the following video.
Like I say, it’s fascinating stuff.
And while it won’t produce an FDA approved flu drug anytime in the near future, research like this helps show us how the immune system works, and that in turn opens up new avenues of exploration for tomorrow's drugs.