That research has now earned OMRF a $2.1 million grant from the National Institutes of Health. Led by Florea Lupu, Ph.D., the four-year project will examine new treatment strategies for sepsis.
Sepsis begins when an infection such as pneumonia, bacterial meningitis or food poisoning enters the bloodstream. The body responds by calling in an overwhelming, system-wide counterattack. But this immune response—sepsis—often proves as devastating as the infection itself, causing tissue death and multiple organ failures. Nearly one-third of all patients who develop sepsis die.
“The immune system is a powerful force—sometimes too powerful for our own good,” Lupu said. “The biggest danger in sepsis is not the blood poisoning, which is serious, but in the immune system response to the poisoning which can kill the patient while trying to destroy the infection.”
One of the first lines of defense is called the complement system, a part of the immune system that helps antibodies and other cells to clear pathogens. But, said Lupu, this system can also cause problems when it’s deployed.
“Instead of a targeted attack, the complement system hits everything. It can literally punch holes in cells, even though they’re not a part of the infection,” he said. “When those cells die and break open, it can cause a cascade of organ failures in sepsis patients.”
In this new project, Lupu is collaborating with Gary Kinasewitz, M.D., at the University of Oklahoma Health Sciences Center and John Lambris, Ph.D., of the University of Pennsylvania to test a therapeutic agent they believe will avoid tissue damage and organ failure.
“We have studied the use of antibodies to stop the histones, but the side effect seems to be that it exacerbates cellular damage,” Lupu said. “We think if we use antibodies in tandem with this new therapy, we can lessen the initial damage in sepsis patients and help more people survive.”