LATE-BREAKING ABSTRACT: Plasma level of TRAIL is associated with severity of sepsis and predicts survival after critical illness

Abstract

Introduction Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that induces cell death by apoptosis or necroptosis. Based on older criteria, lower plasma TRAIL has been associated with increased severity of sepsis in humans. Suppression of TRAIL may promote the dysregulated immune response seen in sepsis.

Methods Subjects admitted to the medical intensive care unit (MICU) at New York-Presbyterian Hospital/Weill Cornell Medicine were recruited in an ongoing, prospective, cohort study. Demographics and clinical outcomes were recorded. We collected plasma on Day 1 of MICU admission. Subjects were stratified by non-infectious critical illness, sepsis, and septic shock using new Sepsis-3 criteria. Plasma TRAIL level was assessed by ELISA using a commercially available kit (R&D Systems, USA).

Results We analyzed the first 79 subjects with available plasma. Median plasma TRAIL concentrations were lower in subjects with septic shock (14.354 pg/mL) compared to control subjects without documented infection (34.342 pg/mL), p=0.008. There was a trend towards lower TRAIL concentration in septic patients without shock (20.307 pg/mL) compared to the same controls, p=0.077, and a trend towards lower median TRAIL concentration in subjects who died at 28 days compared to survivors (14.837 pg/mL vs 21.333 pg/mL, p=0.079). The mean TRAIL level in the cohort was 27.039 pg/mL. Subjects with a TRAIL above the mean had a lower odds of death, OR 0.108 (95% CI 0.013 to 0.873).

Conclusion Soluble TRAIL is lower in patients with septic shock compared to control subjects without documented infection based on new Sepsis-3 criteria. Elevated TRAIL may be predictive of survival.