Inhibition of Interleukin-40 prevents multi-organ damage during sepsis by blocking NETosis.
Summary
Two independent sepsis cohorts showed elevated IL-40 at admission correlating with PCT, CRP, lactate/LDH, and SOFA, enabling early-death stratification. Genetic IL-40 inhibition/knockout reduced NETosis and mitigated multi-organ damage in experimental sepsis, indicating IL-40 as both a prognostic biomarker and therapeutic target.
Key Findings
- IL-40 levels at admission were elevated in two independent sepsis cohorts and correlated with PCT, CRP, lactate/LDH, and SOFA.
- IL-40 enabled stratification of early death risk among critically ill sepsis patients.
- Genetic inhibition/knockout of IL-40 reduced NETosis and attenuated multi-organ injury in experimental sepsis.
Clinical Implications
IL-40 measurement could aid early risk stratification; anti–IL-40 strategies or NETosis-targeted interventions warrant clinical investigation for organ-protective effects.
Why It Matters
Bridges clinical biomarker discovery with mechanistic validation linking IL-40 to NETosis and organ injury, opening a targeted therapeutic avenue in sepsis.
Limitations
- Sample sizes and detailed cohort methodologies are not specified in the abstract
- Therapeutic efficacy is shown preclinically; causal benefit in humans remains unproven
Future Directions
Validate IL-40 prognostic thresholds in multicenter cohorts; develop and test IL-40/NETosis-targeted agents in early-phase sepsis trials.
Study Information
- Study Type
- Cohort
- Research Domain
- Pathophysiology
- Evidence Level
- II - Two independent clinical cohorts with mechanistic validation in animal models
- Study Design
- OTHER