Researchers in Asia point to better sepsis treatments

[kkmalaysia]

A compound that stops inflammation in septic mice has therapeutic potential for treating sepsis in humans.

The compound blocks a crucial inflammatory enzyme called sphingosine kinase 1 (SphK1) that becomes elevated during sepsis and, in the process, prevents multiple organ failure, which can be lethal.

Sepsis, which occurs when bacteria enter the bloodstream and cause global inflammation, is one of the most significant causes for intensive care unit (ICU) admittance. Of patients who experience septic shock (extremely low blood pressure) in the ICU, up to 50 percent will die.

“The body is trying to fight this infection, but in doing so it’s actually destroying a lot of our tissue in key organs like the lungs, liver and kidneys,” said lead researcher, Associate Professor Alirio Melendez, of the Department of Physiology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS).

Because the infection-fighting white blood cells are busy attacking inflamed organs, the body is left vulnerable to further infection by other bacteria.

Currently, antibiotics are the go-to treatments for sepsis, but Melendez said these are insufficient. Even when patients who go into septic shock recover, they have poor quality of life due to extensive organ damage and are susceptible to infection for up to a year because their bodies have grown tolerant to the medications.

Mice with induced sepsis showed time-dependent responses to treatment with SphK1 inhibitors. After 2, 6, 8 and 12 hours, treatment conferred 100 percent, 60 percent, 30 percent and 10 percent protection, respectively. After 12 hours, there was no possibility of rescue. [Science 2010;328(5983):1290-4]

SphK1 inhibitors reduce inflammatory response and the resulting organ damage, which keeps important infection-fighting molecules in the bloodstream.

“We are doing two things in parallel, which antibiotics alone cannot do and other standard therapies cannot do,” Melendez said. “We stop inflammation in key organs like the liver and lungs and let the [white blood] cells be in the place where they can combat bacteria, which is in the blood stream.”

The researchers combined the inhibitor with low doses of antibiotics to fight off infection without further damaging organs.

“The approach is to make a decisive kill and manage runaway inflammatory response,” said co-investigator Associate Professor Koh Dow Rhoon, of the Department of Physiology at the NUS Yong Loo Lin School of Medicine. �Source: Medical Tribune