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."

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