• José Garnacho-Montero, Inmaculada Palacios-García, Ana Díaz-Martín, Antonio Gutiérrez-Pizarraya, José M López-Sánchez, Elísabet Alcocer Gómez, and Mario D Cordero.
• Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Seville, Spain.
• Shock. 2020 Sep 1; 54 (3): 294-300.

IntroductionInflammasomes 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.MethodsProspective 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).ResultsFifty-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.ConclusionsNLRP3 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.

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