Inflammasomes in sepsis

Sepsis remains the primary cause of deaths in intensive care units of hospitals, and although several improvements in clinical management protocols have improved survival rates from sepsis, there are no reliable biomarkers for prognosis or therapies that can treat the pathophysiological bases of the disease. During the initial phases of sepsis there is a strong inflammatory response involving different inflammasomes. In particular, NLRP3, NLRC4, NLRP6, AIM2, and the non-canonical inflammasome are involved in the production of proinflammatory cytokines during sepsis. Although the production of these cytokines can damage different tissues and organs in the host and lead to organ failure and early death from sepsis, most septic patients develop an antiinflammatory response in which the immune system is deactivated. This immunoparalysis is an early response produced when there is an increase in the patient's proinflammatory mediators and affects, among other pathways, the activation of the NLRP3 inflammasome. Septic patients with an early deactivation of NLRP3 present more sepsis-related complications and higher mortality, therefore treatments that boost the immune system of these patients have emerged as novel approaches to reducing mortality from sepsis.