A therapy that blocks an immune-regulating protein could pave the way for a new class of drugs to save lives from sepsis or septic shock, according to a recent study.

In a report published in the August issue of the Journal of Leukocyte Biology, the therapy was able to almost double the survival rate of mice with sepsis, while reducing cell death.

The therapy, which blocks Programmed Death 1, or PD-1, a cell membrane protein, is already being studied in clinical trials to help fight cancer and hepatitis C.

"It could really be something useful clinically," said Dr. Steven Opal, professor of medicine at Brown University and the Infectious Disease Society of America’s representative for the Surviving Sepsis campaign. "What’s nice about it is, it’s a new way to approach the problem, and the situation with septic shock is one where we really need new ideas."

Sepsis, known colloquially as "blood poisoning," is a massive inflammatory response to severe bacterial infection, and a leading cause of mortality in patients after surgery. It can also lead to septic shock--dangerously low blood pressure that can result in multiple organ failure and death.

Someone dies from sepsis once every two and a half minutes, according to the Sepsis Alliance, a charity, and more than 210,000 people die from it in the United States every year, making it the third leading cause of death nationwide, according to some accounts. Treatment costs are upward of $17 billion.

Currently, the only U.S. Food and Drug Administration-approved therapy is activated protein C, which only has a "modest effect on survival," according to immunologists Sanna M. Goyert and Jack Silver, in their accompanying editorial.

Patients with sepsis first undergo a "cytokine storm," or hyperinflammation. Under current standards of care, most patients survive the first stage, the researchers from Washington University School of Medicine in St. Louis, Miss., led by Dr. Richard S. Hotchkiss, wrote in their article. But the patients sometimes then die during the following period of severe immunosuppression called "immune paralysis," in which the original infection and secondary infections overwhelm the patient.

And that's where blocking PD-1 might help.

According to the researchers, PD-1 is known to suppress some immune responses, and help regulate T cells. This can be beneficial: for instance, knockout mice lacking PD-1 can develop lupus-like autoimmune diseases, likely because of uncontrolled immune activity, the authors said. But in experiments, these PD-1-free mice also show resistance to sepsis.

To see if blocking PD-1 would help normal mice with sepsis, the authors first surgically injured the animals' guts, causing peritonitis, to give them a condition that resembles a burst appendix. Next, they injected some with antibodies that interfere with PD-1, and others with saline or inactive antibodies that don't block PD-1.

The researchers found mice with peritonitis who had the treatment within the first 24 or 48 hours had improved seven-day survival. About 70.6 percent lived, against just 33.3 percent getting saline or just 28.6 percent getting inactive antibodies alone.

Treating with the PD-1-blocking antibodies also prevented death of spleen and immune cells, when they were analyzed later, such that the "absolute values in septic mice treated with anti-PD-1 were not statistically different from the sham-treated mice," who never got the rupture-surgery, the authors wrote.

It also prevented cell death from apoptosis, or cell suicide, as analyzed by standard TUNEL and active caspase-3 assays, the researchers wrote.

Still, the authors note there's fear that prolonged treatment with anti-PD-1 antibodies, some of which are currently in Phase II and III trials for cancer, could cause autoimmune reactions. But the authors of the study say in patients with sepsis this is unlikely to be a problem.

"Given the fact that patients with sepsis would not need prolonged therapy with anti-PD-1/anti-PD-L1 antibodies, the concerns for development of autoimmunity would be much diminished," they write.

Even if safe, the treatment likely would have to be used in combination with others. In their editorial, Goyert and Silver note that immunosuppression in sepsis patients can actually be beneficial, and treatments that block some immune and inflammatory activity have also promoted survival.

"Thus, it may be that neither generalized activation nor suppression of the immune system can be the panacea for all sepsis patients," they write, "but rather, the restoration of the delicate balance that normally exists between the active and suppressor arms of the immune system."

Opal concurs that for blocking PD-1, doctors need to know when to do it.

"Undoubtedly this has survived evolution for some purpose, and there must be something good about PD-1, so timing is key in everything, including acute systemic inflammation," he said. "This would be a rescue therapy, for patients already in the throes of a severe illness, as opposed to something you’d give as a preventive. But we really need things to rescue patients who are severely ill."

And though research is ongoing for anti-PD-1 therapies for cancer, it still might be some time before it reaches clinical trials for helping against sepsis. Opal believes many biotechnology and pharmaceutical companies have been burned by "spectacular failures" in sepsis research.

"We have to convince companies it’s still a viable market," he said. "I don’t wish to suggest there are not obstacles -- there certainly are. But I think the advantage of this strategy, is it's a new way of looking at treatment."