• Tiffanie K Jones, John P Reilly, Brian J Anderson, Todd A Miano, Thomas G Dunn, Ariel R Weisman, Roseline Agyekum, Rui Feng, IttnerCaroline A GCAGDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., ShashatyMichael G SMGSDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., and Nuala J Meyer.
• Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
• Shock. 2022 Jan 1; 57 (1): 414741-47.

BackgroundMatrix Metalloproteinases (MMP) respond to tissue damage during sepsis. Higher plasma concentrations of MMPs and the tissue-inhibitor of matrix metalloproteinases (TIMP) have been reported in sepsis compared with healthy controls. The objective of this study was to examine if plasma levels of MMP-3, MMP-9, and TIMP-1 associate with mortality and organ dysfunction during sepsis.MethodsWe conducted a prospective cohort study of critically ill patients with sepsis adjudicated per Sepsis-3 criteria at a tertiary academic medical center. We measured plasma concentrations of MMP-3, MMP-9, and TIMP-1 on intensive care unit admission. We phenotyped the subjects for shock, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality at 30 days. We used logistic regression to test the associations between the MMPs and TIMP-1 with shock, ARDS, AKI, and mortality.ResultsHigher plasma TIMP-1 levels were associated with shock (odds ratio [OR] 1.51 per log increase [95% CI 1.25, 1.83]), ARDS (OR 1.24 [95% CI 1.05, 1.46]), AKI (OR 1.18 [95% CI 1.01, 1.38]), and mortality (OR 1.20 [95% CI 1.05, 1.46]. Higher plasma MMP-3 concentrations were associated with shock (OR 1.40 [95% CI 1.12, 1.75]) and mortality (OR 1.24 [95% CI 1.03, 1.48]) whereas MMP-9 levels were not associated with outcomes. Higher plasma TIMP-1 to MMP-3 ratios were associated with shock (OR 1.41 [95% CI 1.15, 1.72], P = 0.02).ConclusionElevated plasma concentrations of TIMP-1 associate with organ dysfunction and mortality in sepsis. Higher plasma levels of MMP-3 associate with shock and mortality. Plasma MMP and TIMP-1 may warrant further investigation as emerging sepsis theragnostic biomarkers.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.

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