UK Scientist Awarded $3 Million NIH Grant to Study Therapy for Sepsis

Xiang-An Li, Ph.D., of the University of Kentucky Saha Cardiovascular Research Center and Department of Pediatrics, has been awarded a $3 million grant from the National Institutes of Health to study synthetic HDL (sHDL) as a potential therapy for sepsis.

Sepsis -- also called septicemia -- is a life-threatening condition caused by an overwhelming immune response to infection. Immune chemicals released by the body into the bloodstream to fight the infection trigger widespread inflammation that can damage multiple organ systems. In the worst cases, blood pressure drops, the heart weakens and the patient spirals toward septic shock and death.

Sepsis is a major health issue, claiming more than 215,000 lives annually in the United States alone. Anyone can develop sepsis, but it's most common and most dangerous in older adults or those with weakened immune systems. Early treatment of sepsis, usually with antibiotics and large amounts of intravenous fluids, improves chances for survival.

In previous research Li, a pioneer in studying the role of HDL and its receptor SR-BI in sepsis, demonstrated that mice deficient in HDL were highly susceptible to sepsis. In a cooperative study with Dr. Theodore Standiford, chief of the Division of Pulmonary & Critical Care Medicine of the University of Michigan, Li's lab found that HDL levels decrease by 40-70 percent in septic patients, and are associated with a poor prognosis.

Alan Daugherty, Ph.D., director of the UK Saha Cardiovascular Research Center, emphasizes the importance of Li's findings. "These studies suggest that low HDL is a risk factor for sepsis," he said. “HDL is a protective factor in cardiovascular disease and raising circulating HDL levels may provide multiple protections against sepsis.”

More than 100 clinical trials targeting inflammatory or coagulation pathways in sepsis have failed. "These failures teach us that sepsis is a complex disease and more innovative approaches targeting multiple factors are required," Li said. “HDL (high density lipoprotein) is likely a great candidate to achieve this goal."

Li will partner with Anna Schwendeman, Ph.D., an expert in synthetic HDL from the University of Michigan, to promote HDL functions by the use of synthetic HDL as a therapy for sepsis.

"The Agency for Healthcare Research and Quality lists sepsis as the most expensive condition treated in U.S. hospitals, costing more than $20 billion in 2011," said Li. “We hope that this preclinical study will provide a body of data in support of a synthetic HDL-based therapeutic approach for treatment of sepsis and position it for rapid clinical translation.”

Dr. Xiang-An Li laboratory web page:
R01GM113832, National Institute of General Medical Sciences