Protein pathway protects vessels from leaking fluid after inflammation: study

Treating virulent influenza, sepsis, and other potentially deadly infections long has focused on looking for ways to kill viruses and bacteria. But new research from the University of Utah and Utah State University shows that modulating the body's own overeager inflammatory response to infection may help save more lives.

In a study published March 17 in Science Translational Medicine, researchers led by U of U cardiologist Dean Y. Li, M.D., Ph.D., professor of internal medicine and director of the molecular medicine program, shows that protecting blood vessels from hyper-inflammatory response to infection reduced mortality rates in mouse models of avian flu and sepsis by as much as 50 percent. Specifically, the researchers identified a protein signaling pathway, Robo4, that when activated prevents inflammation from weakening blood vessels, which causes them to leak and can result in life-threatening organ damage.

The findings raise the possibility of new broad-range therapies that could be rapidly implemented by public health agencies to fight both viral and bacterial infections, such as pandemic influenza and sepsis, and even potentially deadly human-made biological agents that could cause widespread illness and death, according to Li. Such therapies would be given along with antibiotics, antivirals, and other drugs.

"By blocking the ill effects of inflammation on the host or patient by stabilizing blood vessels, we have identified an entirely different strategy to treat these infections," Li said. "In essence, we've shown that rather than attacking the pathogen, we can target the host to help it to fight infections."

While this study proves the concept of controlling the effects of inflammation to fight the effects of serious infection, developing therapies for people will take years.

Inflammation is a powerful weapon in the body's immune system; without this inflammation, patients would not be able to fight infection. But it's also a double-edged sword.
 
When biochemical mediators, called cytokines, are released in massive quantities as part of the inflammatory response, they can destabilize blood vessels, resulting in leakage, tissue edema (swelling), and in extreme cases, organ failure and death.