Amyloid-β and caspase-1 are indicators of sepsis and organ injury.

Background

Sepsis is a life-threatening condition that results from a dysregulated host response to infection, leading to organ dysfunction. Despite the prevalence and associated socioeconomic costs, treatment of sepsis remains limited to antibiotics and supportive care, and a majority of intensive care unit (ICU) survivors develop long-term cognitive complications post-discharge. The present study identifies a novel regulatory relationship between amyloid-β (Aβ) and the inflammasome-caspase-1 axis as key innate immune mediators that define sepsis outcomes.

Methods

Medical ICU patients and healthy individuals were consented for blood and clinical data collection. Plasma cytokine, caspase-1 and Aβ levels were measured. Data were compared against indices of multiorgan injury and other clinical parameters. Additionally, recombinant proteins were tested

Results

Plasma caspase-1 levels displayed the best predictive value in discriminating ICU patients with sepsis from non-infected ICU patients (area under the receiver operating characteristic curve=0.7080). Plasma caspase-1 and the Aβ isoform Aβx-40 showed a significant positive correlation and Aβx-40 associated with organ injury. Additionally, Aβ plasma levels continued to rise from time of ICU admission to 7 days post-admission.

Conclusions

Aβx-40 and caspase-1 are potentially useful early indicators of sepsis and its attendant organ injury. Additionally, Aβx-40 has emerged as a potential culprit in the ensuing development of post-ICU syndrome.

Informations de copyright

Copyright ©The authors 2024.

Déclaration de conflit d'intérêts

Conflict of interests: All authors have verified there are no conflicts of interest.