HMGB1 and IL-33 kinetics in trauma and hemorrhagic shock: A prospective study in trauma patients
Year: 2020
Type: dissertation
Study design: Observational Study
Abstract: Victims of major trauma run a considerable risk of death even if they arrive in hospital alive. In part this mortality is due to detrimental systemic inflammation leading to failure of organs not initially injured. Unbridled inflammation is the result of innate immune system activation, incited by proteins referred to as “alarmins” being passively released from mechanically damaged cells, or secreted from activated immune cells. Alarmins are constitutively expressed and harbor important housekeeping functions. However, once released to the extracellular space, alarmins acquire a new identity to serve as powerful mediators of inflammation.\nThe main goal of this research was to obtain high-resolution data on the release pattern of two alarmins, HMGB1 and IL-33, after trauma, and to explore their statistical relationship with patient outcome in terms of remote organ failure. \nHMGB1 and IL-33 kinetics in individual patients were explored in 1094 blood samples from 136 patients with a broad spectrum of injuries and outcomes. We coupled this information to data from the Oslo University Hospital Trauma Registry and we found that a biphasic release of HMGB1 after trauma was strongly associated with unfavorable outcome. IL-33 was undetectable in the majority of patients, although a rapid and transient release of IL-33 was observed in a subset of critically injured patients. Our findings provide new insights regarding proximal mediators of inflammation in the aftermath of trauma and shock, hopefully paving the way for identification of therapeutic targets.
Author: William Ottestad
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3164289581