SEQUENTIAL CHANGES OF NLRP3 INFLAMMASOME ACTIVATION IN SEPSIS AND ITS RELATIONSHIP WITH DEATH

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-1 beta (IL-1 beta) 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-1 beta 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 beta 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.