Article ; Online: The double sides of NLRP3 inflammasome activation in sepsis.
Clinical science (London, England : 1979)
2023 Volume 137, Issue 5, Page(s) 333–351
Abstract: Sepsis is defined as a life-threatening organ dysfunction induced by a dysregulated host immune response to infection. Immune response induced by sepsis is complex and dynamic. It is schematically described as an early dysregulated systemic inflammatory ... ...
| Abstract | Sepsis is defined as a life-threatening organ dysfunction induced by a dysregulated host immune response to infection. Immune response induced by sepsis is complex and dynamic. It is schematically described as an early dysregulated systemic inflammatory response leading to organ failures and early deaths, followed by the development of persistent immune alterations affecting both the innate and adaptive immune responses associated with increased risk of secondary infections, viral reactivations, and late mortality. In this review, we will focus on the role of NACHT, leucin-rich repeat and pyrin-containing protein 3 (NLRP3) inflammasome in the pathophysiology of sepsis. NLRP3 inflammasome is a multiproteic intracellular complex activated by infectious pathogens through a two-step process resulting in the release of the pro-inflammatory cytokines IL-1β and IL-18 and the formation of membrane pores by gasdermin D, inducing a pro-inflammatory form of cell death called pyroptosis. The role of NLRP3 inflammasome in the pathophysiology of sepsis can be ambivalent. Indeed, although it might protect against sepsis when moderately activated after initial infection, excessive NLRP3 inflammasome activation can induce dysregulated inflammation leading to multiple organ failure and death during the acute phase of the disease. Moreover, this activation might become exhausted and contribute to post-septic immunosuppression, driving impaired functions of innate and adaptive immune cells. Targeting the NLRP3 inflammasome could thus be an attractive option in sepsis either through IL-1β and IL-18 antagonists or through inhibition of NLRP3 inflammasome pathway downstream components. Available treatments and results of first clinical trials will be discussed. |
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| MeSH term(s) | Humans ; Inflammasomes ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein ; Sepsis ; Cell Death |
| Chemical Substances | Inflammasomes ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein |
| Language | English |
| Publishing date | 2023-03-01 |
| Publishing country | England |
| Document type | Review ; Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 206835-7 |
| ISSN | 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221 |
| ISSN (online) | 1470-8736 |
| ISSN | 0301-0538 ; 0009-0360 ; 0143-5221 |
| DOI | 10.1042/CS20220556 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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