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A different approach to treating sepsis
6/13/2018
 
A small clinical trial at Washington University School of Medicine in St. Louis shows that a drug that revs up the immune system holds promise in treating sepsis. The approach goes against the grain of earlier strategies that have relied on antibiotics and inflammatory medications to tamp down the immune system.

The findings are published March 8 in the journal JCI Insight. “Mortality rates from sepsis have remained essentially the same over the last 50 years,” said senior investigator Richard S. Hotchkiss, MD, a professor of anesthesiology, of medicine, and of surgery. “Hundreds of drugs have been tried and have failed. It may sound counterintuitive when inflammation is such a problem early in sepsis, but our approach is to stimulate certain immune cells to help the patient’s system take control of the infection.”

The trial involved 27 sepsis patients, ages 33 to 82. Although the study was too small to see a statistical benefit in mortality, the researchers noted an improved immune response in patients who were given a drug to beef up their immunity.

The patients were treated with a drug made of interleukin-7 (IL-7), which enhances the proliferation and survival of two types of immune cells: CD4 and CD8. These cells are important because they recruit other immune cells to fight severe infections that can lead to organ failure and death.

The researchers showed that IL-7 boosts adaptive immunity, in which CD4 and CD8 T cells help recruit other immune cells – called macrophages, monocytes, neutrophils and dendritic cells – to kill bacteria that cause infections. Traditional approaches to sepsis therapy do not address the critical problem of patients’ severely compromised immune systems. Without restoring immune function, Hotchkiss said, many patients develop lingering infections and are helpless to fight any new infections.

“We know that 40 percent of patients die in the 30- to 90-day period after the initial septic infection,” Hotchkiss said. “Their bodies can’t fight secondary infections, such as the blood infections and staph infections that can develop later on because their immune systems are shot. By strengthening adaptive immunity with IL-7 and increasing the numbers of CD4 and CD8 cells available to help fight infections, we think this approach can make a big difference.”