Sepsis-Induced Immune Paralysis Reversed by β-Glucan - European Medical Journal


Sepsis-Induced Immune Paralysis Reversed by β-Glucan

2 Mins

SEPSIS is a life-threatening condition with inefficient treatment options available at present. With an incidence of approximately 2–30 per 10,000 people in the Western world and 20% of patients dying in the intensive care unit (ICU), researchers at Radboud University, Nijmegen, Netherlands, investigated the mechanisms involved at an epigenetic, molecular level to help improve these odds and advance understanding of the condition.

A vital constituent of good health, 30–40% of patients successfully treated for sepsis will suffer additional weeks or months with a compromised immune system; this presents the ideal opportunity for secondary infections to take hold, contributing significantly to the high associated death rate. Monocytes within the body are extremely important for the detection and clearance of foreign invaders. In blood poisoning, these phagocytic leucocytes are exposed to lipopolysaccharide (LPS) sugar chains protruding from the outer membranes of Gram-negative bacteria. As a result, LPS-induced toll-like receptor signalling suppresses the differential capability of monocytes into macrophages through functional reprogramming leading to vulnerability of the immune system, a process termed sepsis-induced immunosuppression.

Interestingly, collaboration between Prof Henk Stunnenberg, Full Professor of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, Netherlands, and Prof Mihai Netea, Head of the Division of Experimental Medicine, Department of Internal Medicine, Radboudumc, Radboud University, Nijmegen, Netherlands, and colleagues, found that fungal cell wall component β-glucan had a startlingly different effect on monocytes following exposure: “By adding β-glucan to blood samples of trial subjects with a disabled immune system, the macrophages were re-activated,” explained Prof Stunnenberg. The researchers found that through distal element histone modification and transcriptional reactivation of unresponsive genes, the capacity for beneficial cytokine production was restored.

A part of the BLUEPRINT project, a 5-year project co-operated by 54 research teams across Europe, this study reinstated the growing importance of epigenetic regulation in host processes. Prof Netea alluded to subsequent research ventures: “A clinical trial with patients is an obvious step for the near future. We could begin with blood samples of people who have been admitted to the ICU with sepsis.”