%V 54
%T Sequential Changes of NLRP3 Inflammasome Activation in Sepsis and its Relationship With Death
%D 2020
%N 3
%A José Garnacho-Montero
%A Inmaculada Palacios-García
%A Ana Díaz-Martín
%A Antonio Gutiérrez-Pizarraya
%A José M. López-Sánchez
%A Elísabet Alcocer Gómez
%A Mario D. Cordero
%K Caspase-1;  Caspase-3;  inflammation ; Mortality; NLRP3 inflammasome NLRP3 inflammasome;  Sepsis.
%J Shock
%X Introduction: 
Inflammasomes are recognized as key components of the innate immune response in sepsis. We aimed to describe the transcriptional expression of nucleotide-binding domain, leucine-rich repeat–containing receptor, pyrin domain–containing-3 (NLRP3), and serum interleukin-1β (IL-1 β) in critically ill patients, their changes over the first week and their prognostic value in septic patients.

Methods: 
Prospective study including patients with sepsis based on Sepsis-3 definitions and a control group of critically ill patients without sepsis. We measured the circulating levels of IL-1β as well as the transcriptional expression of NLRP3 at admission and on days 3 and 7. Caspase-1 and caspase-3 activation was analyzed in a matched cohort of patients with septic shock (four dead and four survivors).

Results: 
Fifty-five septic patients and 11 non-septic patients were studied. Levels on day 0 and 3 of IL-1 β and NLRP3 inflammasome expression were significantly higher in patients with sepsis than in controls. NLRP3 was significantly higher in septic patients who survived at day 7 without significant difference between survivors and non-survivors at baseline and on day 3. In survivors, an increased caspase-1 protein expression with reduced expression caspase-3 was observed with the opposite pattern in those who died.

Conclusions: 
NLRP3 is activated in critically ill patients but this up-regulation is more intense in patients with sepsis. In sepsis, a sustained NLRP3 activation during the first week is protective and sepsis. An increased caspase-1 protein expression with reduced expression caspase-3 is the pattern observed in septic shock patients who survive.
%R doi:10.1097/SHK.0000000000001521
%L uneatlantico119
%P 294-300