This study demonstrates that elevated serum matrix metalloproteinase-8 (MMP-8) levels measured at ICU admission are strongly associated with increased 28-day mortality in sepsis patients. Baseline MMP-8 improves prognostic accuracy beyond established clinical scores such as SOFA and lactate.
Background
Sepsis is a leading cause of early mortality in intensive care units, and early biomarkers reflecting injurious inflammatory activation are needed to improve risk stratification. MMP-8, a neutrophil-derived collagenase, contributes to extracellular matrix degradation and tissue injury during inflammation. Its prognostic relevance at ICU admission in sepsis has not been well established. This study evaluated whether admission serum MMP-8 levels predict 28-day mortality in a cohort of sepsis patients.
Data Highlights
Parameter
Value
Number of patients
274
28-day deaths
69
Hazard ratio per 10 ng/mL MMP-8 (unadjusted)
1.40 (95% CI 1.29–1.51)
Hazard ratio per 10 ng/mL MMP-8 (adjusted)
1.34 (95% CI 1.23–1.47)
Adjusted HR highest vs. lowest MMP-8 tertile
6.50 (95% CI 2.62–16.14)
AUC for SOFA + lactate
0.754
AUC for SOFA + lactate + MMP-8
0.867 (P < 0.001)
Key Findings
Higher baseline serum MMP-8 levels at ICU admission are independently associated with increased 28-day mortality in sepsis patients.
There is a graded dose–response relationship between MMP-8 tertiles and mortality risk, with the highest tertile showing a 6.5-fold increased adjusted hazard.
Serial MMP-8 measurements remain elevated in non-survivors during the first week of ICU stay.
The prognostic association of MMP-8 is stronger in patients with admission lactate ≥ 4 mmol/L, indicating interaction with tissue hypoxia severity.
Adding MMP-8 to established clinical risk models significantly improves mortality prediction accuracy (AUC increase from 0.754 to 0.867).
MMP-8 likely reflects maladaptive neutrophil-driven inflammatory injury rather than sepsis-specific pathology.
Clinical Implications
Measuring serum MMP-8 at ICU admission may provide valuable early prognostic information to identify sepsis patients at high risk of short-term mortality. Incorporation of MMP-8 into existing clinical risk models could enhance risk stratification and guide more tailored management strategies. However, external validation and comparison with other inflammatory biomarkers are needed before routine clinical implementation.
Conclusion
Baseline serum MMP-8 is a promising biomarker reflecting inflammatory injury severity that independently predicts 28-day mortality in sepsis patients admitted to the ICU. Its addition to clinical models improves prognostic discrimination, supporting further validation studies.
References
Sepsis-3 Criteria Reference
Matrix Metalloproteinase-8 Role in Inflammation [2]
Lactate and Tissue Hypoxia in Sepsis [3]
MMP-8 Polymorphisms and Sepsis Susceptibility [4]
Validation and Clinical Utility of MMP-8 in Sepsis [5]
