Role of inflammasomes in acute respiratory distress syndrome.
Summary
This state-of-the-art review positions neutrophil inflammasomes—particularly NLRP3—as central hubs linking DAMP/PAMP signals to IL-1β/IL-18 maturation in ARDS. It synthesizes evidence across inflammasome families, explains translational failures, and outlines biomarker-guided immunomodulatory strategies for future trials.
Key Findings
- Positions NLRP3 as the most implicated inflammasome in both infectious and sterile ARDS.
- Highlights roles of NLRC4 and AIM2 inflammasomes and inflammasome-independent pathways.
- Explains translational gaps: rodent benefits of IL-1β/IL-18/inflammasome blockade have not translated to humans, likely due to neutrophil biology.
- Proposes biomarker-guided, neutrophil-focused immunomodulation for future trials.
Clinical Implications
While standard supportive ARDS care remains unchanged, clinicians should consider phenotyping patients for inflammasome activity and IL-1β/IL-18 axes, and watch for trials of NLRP3 or IL-1 pathway inhibitors. Avoid indiscriminate immunosuppression; target based on biomarkers and timing.
Why It Matters
It reframes ARDS pathogenesis around neutrophil inflammasomes and provides a roadmap for targeted interventions, addressing a historic lack of effective pharmacotherapy. The synthesis is likely to guide both mechanistic studies and early-phase trials.
Limitations
- Narrative (non-PRISMA) review without systematic search/selection methods.
- Heavy reliance on rodent models; limited human mechanistic validation.
Future Directions
Develop human ARDS biomarkers of inflammasome activation (e.g., neutrophil-specific readouts), integrate single-cell/functional assays, and test NLRP3/IL-1 pathway inhibitors in biomarker-enriched, adaptive trials.
Study Information
- Study Type
- Systematic Review
- Research Domain
- Pathophysiology
- Evidence Level
- V - Narrative, non-systematic expert review without new primary data
- Study Design
- OTHER