UF researchers hope clinical trial will lead to new sepsis treatment

GAINESVILLE, Fla. — University of Florida researchers are part of a nationwide clinical trial to evaluate whether an anti-cancer medication can be effective against sepsis and septic shock.

Sepsis is thought to blunt the immune system in ways similar to some kinds of cancer through PD-1, a protein emitted by certain cells in the body. Nivolumab, an immunotherapy drug approved by the Food and Drug Administration to treat patients with certain types of non-small cell lung cancer and other types of the disease, blocks PD-1 in cancer patients and helps the immune system recognize and destroy diseased tissue.

The clinical trial seeks to determine whether blocking PD-1 can also boost the immune system in patients with severe sepsis or septic shock. UF is the only center in Florida, and one of four in the Southeast, recruiting participants.

“Think of your immune system as a crackling fire, burning at a steady pace. Sepsis is like throwing gasoline on that fire. You get a huge flare and explosion but afterward, you are left with smoldering coals that do not work. The point is to get those smoldering coals back to a crackling fire again,” said UF’s lead investigator, Scott C. Brakenridge, M.D., MSCS, FACS, an assistant professor of surgery and anesthesiology in the UF College of Medicine’s division of acute care surgery.

Sepsis is an illness or complication in which the body has a severe, overwhelming response to infection. That response can induce tissue damage, organ failure and death. What differentiates sepsis from infection is the significant host response to an infectious virus, bacteria, fungus or parasites.

“Instead of trying to blunt that immune explosion, we are focusing on ways to get the immune system back on its feet after it’s been knocked down,” Brakenridge said. “The goal is to prevent prolonged immunosuppression so the body can fight infectious challenges.”

Sepsis is the most expensive condition treated in U.S. hospitals, with annual costs exceeding $20 billion, according to the Agency for Healthcare Research and Quality.

“The early care of sepsis has improved dramatically, and in-hospital mortality has decreased substantially. The majority of sepsis survivors progress into chronic critical illness characterized by prolonged stays on intensive care units, cognitive and functional disabilities, sepsis relapse, discharge to long-term health care or rehabilitation facilities, and death,” said Frederick A. Moore, M.D., FACS, MCCM, the program director of the UF Sepsis and Critical Illness Research Center and a professor and chief in the division of acute care surgery in the UF College of Medicine.

Specifically, UF Health clinical and basic science researchers recognized a new predominant type of chronic critical illness that is occurring with an increased frequency in surgical ICUs — persistent inflammation, immunosuppression and catabolism syndrome — for which there are no effective interventions and clinical outcomes are poor.

The UF College of Medicine recently approved a designated Sepsis and Critical Illness Research Center. The center stems from a UF department of surgery-led initiative established in 2014 through a $12 million grant from the National Institutes of Health, and builds on clinical and translational research that began with the original sepsis research program.