Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
JCI Insight ; 4(9)2019 05 02.
Article in English | MEDLINE | ID: mdl-31045578

ABSTRACT

BACKGROUND: In sepsis, there may be dysregulation in programed cell death pathways, typified by apoptosis and necroptosis. Programmed cell death pathways may contribute to variability in the immune response. TRAIL is a potent inducer of apoptosis. Receptor-interacting serine/threonine protein kinase-3 (RIPK3) is integral to the execution of necroptosis. We explored whether plasma TRAIL levels were associated with in-hospital mortality, organ dysfunction, and septic shock. We also explored the relationship between TRAIL and RIPK3. METHODS: We performed an observational study of critically ill adults admitted to intensive care units at 3 academic medical centers across 2 continents, using 1 as derivation and the other 2 as validation cohorts. Levels of TRAIL were measured in the plasma of 570 subjects by ELISA. RESULTS: In all cohorts, lower (<28.5 pg/ml) versus higher levels of TRAIL were associated with increased organ dysfunction (P ≤ 0.002) and septic shock (P ≤ 0.004). Lower TRAIL levels were associated with in-hospital mortality in 2 of 3 cohorts (Weill Cornell-Biobank of Critical Illness, P = 0.012; Brigham and Women's Hospital Registry of Critical Illness, P = 0.011; Asan Medical Center, P = 0.369). Lower TRAIL was also associated with increased RIPK3 (P ≤ 0.001). CONCLUSION: Lower levels of TRAIL were associated with septic shock and organ dysfunction in 3 independent ICU cohorts. TRAIL was inversely associated with RIPK3 in all cohorts. FUNDING: NIH (R01-HL055330 and KL2-TR002385).


Subject(s)
Apoptosis , Biomarkers/blood , Multiple Organ Failure/blood , Sepsis/blood , TNF-Related Apoptosis-Inducing Ligand/blood , Adolescent , Adult , Aged , Cell Death , Critical Illness , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , New York , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Sepsis/mortality , Shock, Septic/blood , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...