Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeting blood vessels, immune system may offer way to stop infection-caused inflammation

18.03.2010
Protein pathway protects vessels from leaking fluid

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. For example, a severe infection such as that of the 1918 pandemic flu, can cause life-threatening lung damage when alveoli become inflamed and fill with fluid, a condition known as lung edema. Similarly, sepsis can damage organs such as the kidneys by weakening blood vessels and allowing fluid to leak into the kidney tissue, impairing its vital functions.

Although it will take much more work to determine if Robo4 can be manipulated to block inflammation in sepsis, influenza, and other infections, the protein's signaling pathway appears to be ideal for stabilizing the endothelial cells that line blood vessels, according to Guy A. Zimmerman, M.D., a U of U professor of internal medicine who investigates inflammation and sepsis. "For this reason, the Robo4 pathway may be more effective and less likely to have negative side-effects than some of the approaches and drugs that have been tried in the past," said Zimmerman, a co-author on the study.

Targeting the pathogens that cause influenza and sepsis has been the primary strategy to fight those infections. While this has been successful, it also has limitations because pathogens can evolve quickly to develop resistance to antibiotics and antiviral medications. A second approach has been to dampen a patient's immune system response to infection. However, past approaches led to poor outcomes in patients, in part because they sometimes increased the sick individual's susceptibility to a second, "opportunistic" infection.

Protecting the host from its own inflammatory response to infection offers a potential strategy to reduce the mortality rate from many different types of serious infections. In the mouse models of this study, the mortality rate for some sepsis and avian flu infections approached 90 percent when left untreated. By protecting blood vessels through activating Robo4, mortality was reduced in some cases to almost half.

Dale L. Barnard, Ph.D., a virus specialist and research associate professor at the Institute for Antiviral Research in the Department of Animal, Dairy and Veterinary Sciences at Utah State University, said the study opens a potentially exciting approach to treating virulent viral-caused infections such as pandemic H1N1 and the highly infectious avian flu. "It may be even a more effective approach if it were to be used in combination with antiviral drug therapy, perhaps allowing the antiviral drug to be used at concentrations below those which would induce drug resistance or allow the drug to be administered for shorter periods of time," said Barnard, also a co-author on the study.

Li's study of Robo4 as an agent for mitigating the effects of inflammation grew from his research into blood vessel formation. In 2003, he cloned Robo4 and showed that it inhibits uncontrolled blood vessel growth, thereby stabilizing vessels and preventing leakage. Robo4 is activated by another protein, called Slit.

Phil Sahm | EurekAlert!
Further information:
http://www.hsc.utah.edu

More articles from Studies and Analyses:

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Disarray in the brain
18.12.2017 | Universität zu Lübeck

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

The world's most powerful acoustic tractor beam could pave the way for levitating humans

22.01.2018 | Power and Electrical Engineering

Siberian scientists learned how to reduce harmful emissions from HPPs

22.01.2018 | Power and Electrical Engineering

Combination of Resistance Genes Offers Better Protection for Wheat against Powdery Mildew

22.01.2018 | Agricultural and Forestry Science

VideoLinks
B2B-VideoLinks
More VideoLinks >>>