Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis
Authors' conclusion
Septic patients had elevated serum IL-36 levels, which may correlate with disease severity and mortality. In experimental sepsis, we demonstrated a previously unrecognized role of IL-36R deletion in increasing lethality.
Study context
- Population
- Septic patients at intensive care unit (ICU) and ED admission; mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis
- Participants
- 47 / 21 / 21
- Comparison
- Sepsis vs ICU controls vs Healthy volunteers
- Sepsisn = 47
- ICU controlsn = 21reference
- Healthy volunteersn = 21reference
- Outcome
- Serum IL-36 level
- Follow-up
- Day of ICU and ED admission
Methodological detailshuman cohort, murine CLP sepsis model
- Human cohort
- Murine CLP sepsis model
Main finding
As reported in the abstract
- Significantly higher serum IL-36 in sepsis vs ICU controls and healthy volunteers; related to sepsis severity
- Lower serum IL-36 in non-survivors vs survivors of sepsis
- High serum IL-36 associated with 28-day mortality; independent predictor by logistic regression
- IL-36R deletion increased lethality in CLP-induced sepsis
Further findings
Bacterial load and organ injury in septic mice
- IL-36R deletion: higher bacterial load and more severe lung, liver and kidney injury
Mechanism
- IL-36R ligands released upon lung damage activated IL-36R+ lung fibroblasts, inducing lipocalin 2, and induced lung epithelial cell apoptosis
Original publication
Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis. Crit Care. Published 13 December 2023. doi:10.
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