The role of NLRP3 inflammasome in sepsis: A potential therapeutic target.

Abstract

Sepsis is the host immune imbalance following infection and leads to organ dysfunction, with highly complicated pathophysiology. To date, sepsis still lacks effective therapies with high mortality rates. Recently, numerous studies have highlighted the potential of NLRP3 inflammasome as a therapeutic target during sepsis. NLRP3 inflammasome is a protein complex that could induce the activation of caspase-1 and the following release of pro-inflammatory cytokines such as IL-1β and IL-18. It was demonstrated that NLRP3 inflammasome was involved in the development and progression of sepsis. In contrast, inhibition of NLRP3 inflammasome activation could mitigate the inflammatory response, protect organ function, and improve outcomes and mortality. This paper illustrated the activation pathways of the NLRP3 inflammasome and its possible molecular mechanisms in the pathophysiology of sepsis. Meanwhile, the beneficial effects of inhibiting NLRP3 activation in sepsis-related organ damage were also presented. In addition, the diverse role of NLRP3 inflammasome in bacterial clearance was addressed. Of note, several herbal extracts targeting NLRP3 inflammasome in the treatment of sepsis were emphasized. We hope that this paper could provide a basis for further drug research targeting NLRP3 inflammasome.