Researchers at Feinstein Institutes Identify Defensive Molecules That Could Worsen Inflammation in Sepsis

Saturday, July 22, 2023

The Feinstein Institutes for Medical Research have made a significant discovery in the study of sepsis, a leading cause of in-hospital deaths worldwide often referred to as a silent killer. Despite claiming over 11 million lives annually globally, there is no single treatment for this deadly condition. However, researchers at the Feinstein Institutes have made a potential breakthrough by identifying a type of white blood cell that can exacerbate inflammation in sepsis, opening up new possibilities for therapeutic research.

The study, led by Professor and Chief Scientific Officer Ping Wang, MD, yielded crucial insights and was published in the Journal of Clinical Investigation. The researchers, including Monowar Aziz, PhD, and Max Brenner, MD, PhD, discovered a new subset of neutrophils, called antigen-presenting aged neutrophils (APANs). Neutrophils are typically the first line of immune defense against infections and play a key role in initiating the inflammatory response. However, the specific subset of APANs was found to be exceptionally inflammatory, capable of causing severe tissue damage upon activation.

Dr. Wang, the senior author of the paper, explained, "APANs, when triggered, can result in devastating circumstances for patients who have sepsis. The discovery of these neutrophils will help researchers and doctors to better understand sepsis and develop new therapies to tackle this condition."

Sepsis occurs when the body's immune system triggers inflammation to combat infections. However, if the inflammatory response becomes uncontrolled, it can lead to damage in multiple organ systems and ultimately result in death. Patients with sepsis often experience the simultaneous occurrence of pro- and anti-inflammatory pathways, leading to immunosuppression, an inability to eradicate invading bacteria, and increased vulnerability to secondary infections.

This study builds upon Dr. Wang's previous research, which highlighted the role of extracellular cold-inducible RNA-binding protein (eCIRP) as a new inflammatory mediator. eCIRPs are alarm molecules released during sepsis that can cause immune dysfunction and disrupt the immune system's cells responsible for ingesting bacteria and releasing pro-inflammatory and antimicrobial mediators, known as macrophages.

The new research revealed a significant increase in the frequency of APANs in the blood, spleen, and lungs of septic mouse models, as well as in the blood of sepsis patients. By transferring APANs to septic mice, researchers observed heightened levels of injury and inflammatory markers, exacerbated acute lung injury, and reduced survival odds, indicating that eCIRPs released during sepsis induced harmful APANs.

In a related effort, last year, Dr. Wang and other co-principal investigators at the Feinstein Institutes received $3.8 million in funding from the National Institute of Health to further study sepsis and radiation exposure, aiming to make further strides in understanding and combating this life-threatening condition.

Harvard Medical School - Leadership in Medicine Southeast Asia47th IHF World Hospital CongressHealthcare Innovation & Transformation SummitHealthcare CNO SummitHealthcare CMO SummitThe Healthcare Patient Experience & Engagement Summit 2024