Abstract
Abstract
Background
The NLRP3 inflammasome is a cytosolic multiprotein complex that serves as a key regulator of innate immunity by reacting to pathogen- and damage-associated signals and orchestrating downstream inflammatory responses. Inflammasome activation induces caspase-1-dependent maturation of interleukin (IL)-1β, IL-18 and gasdermin D, which results in pyroptotic cell death.
Main text
While tightly controlled inflammasome activation is essential for effective host defence and pathogen clearance, accumulating evidence implicates its dysregulation as a central driver of host response imbalance in critical illness. In conditions such as sepsis and acute respiratory distress syndrome, excessive activation contributes to hyperinflammation, endothelial dysfunction, immunothrombosis, and multi-organ failure. Conversely, insufficient or exhausted inflammasome responses may impair microbial clearance and predispose to secondary infections. These observations underscore the context-dependent and temporally dynamic role of inflammasome signalling as being either protective or pathogenic. Emerging therapeutic strategies aim to restore immune homeostasis through targeted modulation of inflammasome pathways, including IL-1 blockade (e.g., anakinra) and inhibition of upstream signalling components. However, clinical translation remains challenging, requiring improved patient stratification, biomarker-guided approaches, and a deeper understanding of disease heterogeneity.
Conclusions
Inflammasome signalling plays a highly dynamic role in critical illness, contributing to effective host defence, if functional, or to pathological inflammation, if dysregulated. Although targeted modulation of inflammasome pathways represents a promising therapeutic strategy, further research is needed to refine patient selection, identify reliable biomarkers, and better characterise disease heterogeneity to enable successful clinical translation.