Sepsis – preventing the “inflammatory reflex”

Sepsis, also known as blood poisoning, is the leading cause of death in intensive care units.   Globally, it causes more than 11 million deaths each year. An innovative approach may hold the key to boosting the recovery of critically ill patients with sepsis, according to new research from a team at the Florey Institute of Neuroscience and Mental Health.

Published in Scientific Reports, the Florey team have demonstrated how preventing the ‘inflammatory reflex’ may help reverse the immunosuppression that often occurs during sepsis.

“Sepsis can be caused by any kind of infection entering the bloodstream and then spreading throughout the  body, including bacterial, viral or fungal infections. The immune system initially reacts to the infection that is causing sepsis with a very strong inflammatory response. However, as the illness progresses the inflammatory response decreases, and this may lead to a period where the body’s own immune defences are depressed. This is a critical period, during which unfortunately many patients die” explained Professor Robin McAllen from the Florey Institute.

Using their knowledge that the brain influences the immune system through a pathway known as the splanchnic sympathetic nerves, the team investigated whether interrupting this channel would have an impact on the resolution of sepsis.

“We know that the brain both ‘listens’ and ‘talks’ to the immune system. In sepsis, the brain sends signals through the splanchnic sympathetic nerves which can damp down the body’s inflammatory response,” said Professor McAllen.

“This is known as the ‘Inflammatory Reflex’ and in most normal situations it is a helpful response. In critical illnesses like sepsis though, it may be unhelpful.”

Studying infection with E.coli bacteria, isolated from a septic patient, in a pre-clinical large animal model, the Florey team showed that surgically cutting the splanchnic nerves prevented the inflammatory reflex from dampening the immune response.

“The results were very rapid. After preventing the ‘inflammatory reflex’, the innate immune mechanisms removed the infection from the bloodstream within 90 minutes, leading to a rapid recovery in the clinical state” said Dr Yugeesh Lankadeva.

“These results have the potential to improve the treatment of patients with sepsis, and ultimately save many lives.”

The research was performed in partnership with researchers from the Peter Doherty Institute, Murdoch Children’s Research Institute, University of Melbourne and University of Bologna. The Florey team recently received funding from the National Health and Medical Research Council of Australia to explore clinically feasible strategies to reverse immunosuppression during the later phases of sepsis from 2020-2023 (GNT1186382).

The study has been published in Scientific Reports. Click here to read the full paper.

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