Anti-inflammatory agent could decrease septic shock mortality

Researchers in Adelaide have discovered a naturally occurring blood protein — a type of corticosteroid-binding globulin (CBG) — that could significantly decrease mortality caused by septic shock. The CBG project is a collaboration between The University of Adelaide, the Royal Adelaide Hospital and medical research charity AusHealth.

Septic shock is an often fatal infection that causes uncontrolled inflammation in the whole body. As explained by CBG project head Professor David Torpy, “Current treatment involves antibiotics and supportive measures such as fluids, ventilation and blood pressure-elevating drugs. But the mortality is still high, leading to death in 30–50% of patients.”

The research team has now identified a type of CBG which they are developing as a revolutionary therapeutic treatment. According to Torpy, “This is the first potentially deliverable, natural anti-inflammatory agent discovered since cortisone was found in 1949.”

CBG is a large molecule responsible for transporting a single (and much smaller) molecule of cortisol, an anti-inflammatory steroid that our bodies produce in times of stress. Reasoning would suggest that an injection of cortisol would reduce uncontrolled inflammation brought on by septic shock and reliably reduce mortality, but Torpy’s team discovered it was the presence of the transporter — the CBG — that directly correlated with the severity of a patient’s illness.

“We observed that the more critical the patient, the lower their levels of CBG,” he said.

“CBG is a big and complex molecule and there are lots of dynamic things about it. I always thought it seemed to too complex and dynamic to simply be a taxi for cortisol.”

Two years ago, the CBG team began trials in mice at the South Australian Health and Medical Research Institute (SAHMRI), where they were able to significantly reduce mortality. Torpy noted that mice react the same as humans to septic shock, so he is “very confident” the outcome can be demonstrated in a human clinical trial, anticipated to start in mid-2026.

“In America alone, hospitals spend US$38 billion annually to treat septic shock,” Torpy noted. “If this clinical trial works even half as well as it works in mice, it would still save half of that expenditure per year.”

Before a clinical trial can begin, the team needs to produce sufficient quantities of the optimal form of CBG. Fortunately, the team has been awarded $1.4 million from the Health Services Charitable Gifts Board to produce the CBG protein at scale.

The funding will go in part to manufacturing CBG using Chinese hamster ovary (CHO) cells, which Torpy anticipates will deliver CBG more cheaply than the present means of production. The researchers are also being assisted by AusHealth to patent the CBG protein and commercialise the new therapy.

Image credit: iStock.com/Love Employee