Use of IL-6 may reduce incidence of hemorrhagic shock
By Ruth SoRelle, M.P.H.
Serious injuries can cause collapse of the body's circulatory system – the system by which blood gets to tissues and organs. Finding a way to prevent that could, in fact, save half the lives currently lost to traumatic injuries, experts estimate.
Now researchers at Baylor College of Medicine said their research indicates that supplementing a potent stimulator of the body's protective systems – interleukin-6 – may help reduce the death-dealing effects of this problem called hemorrhagic shock. Their work appears in the open-access journal PLoS One.
"Traumatic injury is the most common cause of death in people in the most productive years of their lives," said David J. Tweardy, M.D., professor and interim chair of medicine at BCM and senior author of the report. "For those who have survived their severe injury, the next problem is how to make the most of that first 'golden hour' of treatment."
He and his colleagues hope their work with interleukin-6 (IL-6) will point the way.
Saving heart cells
In research in rats, Tweardy and his colleagues found that the heart fails in the condition called hypovolemic circulatory collapse because its cells are undergoing programmed cell death – a process known as apoptosis. As the cells die, the heart does not pump well, the animal's blood pressure drops and cannot be restored to normal.
However, when they gave the animal IL-6, already known to protect against apoptosis in other settings, they found that the heart cells were not dying at the same rate. They could be resuscitated successfully and their mortality was reduced five-fold.
Tweardy hopes to repeat the experiments in larger animals. If they prove successful there, he said that studies in people will follow.
Role of Stat3
Trying to determine how IL-6 worked, Tweardy and his colleagues looked at a master regulator of apoptosis, Stat3 (signal transducer and activator of transcription 3). Stat3 is an intracellular protein activated by IL-6. Stat3 receives a signal from IL-6 binding to the surface of heart cells and takes it to the nucleus where it binds to DNA and alters the program of the cell to prevent cell death.
When Stat3 activation was blocked using a drug developed earlier by Naijie Jing in his group, IL-6 lost its protective effect, said Tweardy.
Others who took part in this research include Jeffrey A. Alten, Ana Moran, Anna I. Tsimelzon, Mary-Ann A. Mastrangelo and Susan G. Hilsenbeck, all of BCM and Valeria Poli of the University of Turin in Italy.
Funding for this work came from the National Heart, Lung and Blood Institute of the National Institutes of Health.
The article can be found at http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18270592
or http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001605
