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.

Source: University of Utah Health Sciences