Human endotoxaemia model
Research type
Research Study
Full title
Does mitochondrial haplogroup predict the inflammatory response in a model of human endotoxaemia?
IRAS ID
164751
Contact name
John Simpson
Contact email
Sponsor organisation
Newcastle upon Tyne Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 2 months, 2 days
Research summary
The healthcare burden from infection remains substantial. Sepsis (a major form of infection) is found in approximately 2% of hospital admissions, half of which require treatment in the intensive care unit (ICU). As many as 30% of patients have sepsis on admission or during their ICU stay. Mortality associated with sepsis is higher than that of other syndromes leading to ICU admission and it is the most common cause of death in non-surgical ICUs. Although sepsis is one of the oldest syndromes recognised within medicine, understanding of its biology remains incomplete. A self-limiting model of human endotoxaemia, induced by the administration of intravenous lipopolysaccharide (LPS), mimics the early stages of sepsis and facilitates investigation, and development of new treatments, in humans.
Risk factors for the development of sepsis are premorbid health status of the host, causative organism, timeliness of medical intervention and host genetic characteristics. Mitochondrial DNA (mtDNA) encodes for essential proteins involved in cellular energy production. Impaired mitochondrial energy production is important in the development of organ dysfunction in sepsis. Individuals can be divided into genetic categories (or haplogroups) based on natural variation in their mtDNA. One of the groups has a known survival advantage over others but the mechanisms that underpin this are unknown. Furthermore, very little is known about the cellular and molecular evolution of inflammation during sepsis.
Thirty healthy volunteers will be recruited. Participants will have baseline blood samples taken and then LPS will be administered and further blood samples taken. Volunteers will attend for blood sampling and follow-up the day after the study and then 7 days following the study. Samples will be used to determine the haplogroup of the individual and the extent of activation of immune cells that fight infection (monocytes and neutrophils) in response to LPS.REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
17/YH/0021
Date of REC Opinion
1 Mar 2017
REC opinion
Further Information Favourable Opinion