The imbalance between matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in acute pancreatitis

Abstract

Background: The balanced activity of matrix metalloproteinases and their tissue inhibitors is an important, albeit still not completely understood, determinant of extracellular matrix homeostasis, a factor involved in the pathogenesis of acute pancreatitis (AP).

Aims: The aim of this study was to compare serum concentrations of matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) in patients with AP of various severity and to investigate their relationship with prognostic indicators of AP severity, e. g., polymorphonuclear leukocyte elastase (PMN-E).

Patients and Methods: The study included 37 patients with mild (n = 18) or severe AP (n = 19) and 15 healthy controls. Serum concentrations of MMP-9 and TIMP-1 were determined on admission (day 1) and on days 2, 3, 5 and 10.

Results: Throughout the study period, the serum MMP-9 concentration in patients with severe AP was significantly higher than those in individuals with mild AP and in healthy controls. In turn, the serum MMP-9 concentrations in persons with mild AP did not differ significantly from those of the controls. The serum TIMP-1 concentrations in both groups were significantly higher than in the controls. Beginning from the 2^nd day of hospital stay, the serum TIMP-1 concentration in patients with severe AP was significantly higher than in individuals with mild AP. There were significant correlations between: MMP-9 and PMN-E, TIMP-1 and PMN-E, and MMP-9 and TIMP-1.

Conclusion: A disturbed balance between MMP-9 and TIMP-1 observed during the early stages of severe AP suggests that endogenous TIMP-1 is unable to prevent excessive activation and release of MMP-9. MMP-9 may represent a new marker of AP severity.

Zusammenfassung

Hintergrund: Eine ausgewogene Aktivität von Matrix Metalloproteinasen (MMPs) und ihrer Inhibitoren (tissue inhibitors of matrix metalloproteinases, TIMPs) ist ein wichtiger determinierender Faktor der extrazellulären Matrixhomöostase, der auch an einem Krankheitsverlauf von akuter Pankreatitis (AP) beteiligt ist.

Ziele: Vergleich der Serumkonzentration von Matrix-Metalloproteinase 9 (MMP-9) und TIMP-1 bei Patienten mit AP unterschiedlichen Schweregrads, die Untersuchung ihres Verhältnisses mit den Belastungsanzeigen, z. B. Granulozyt Elastase (polymorphonuclear leukocyte elastase, PMN-E).

Material und Methodik: Die Untersuchung umfasst 37 Patienten mit leichter AP (N = 18), mit schwerer AP (N = 19) und 15 gesunde Kontrollpersonen. Die Serumkonzentrationen von MMP-9 und TIMP-1 wurden am Anfang, am 2., 3., 5. und 10. Tag der Untersuchung festgestellt.

Ergebnisse: Während der ganzen Untersuchungszeit war die Serumkonzentration von MMP-9 bei Patienten mit schwerer AP erheblich höher als bei Patienten mit leichter AP und bei den gesunden Kontrollpersonen. Im Rahmen der gesamten Untersuchungszeit war der Unterschied zwischen der Serumkonzentration von MMPs bei Patienten mit leichter AP und den gesunden Kontrollpersonen nicht signifikant. Die Serumkonzentrationen von TIMP-1 bei beiden Gruppen von Patienten mit AP waren erheblich höher als bei den gesunden Kontrollpersonen. Ab dem 2. Tag des Krankenhausaufenthalts war die Serumkonzentration von TIMP-1 bei den Patienten mit schwerer AP erheblich höher als bei den Patienten mit leichter AP. Es wurden statistisch wesentliche Korrelationen zwischen MMP-9 und PMN-E; TIMP-1 und PMN-E; und TIMP-1 und MMP-9 festgestellt.

Schlussfolgerung: Das gestörte Gleichgewicht zwischen MMP-9 und TIMP-1, das während des Anfangsstadiums von schwerer AP observiert wurde, suggeriert, dass das endogene TIMP-1 nicht imstande ist, übermäßige Aktivierung und Freistellung von MMP-9 zu verhindern. MMP-9 kann einen neuen Schweregradmarker der AP begründen.

Schlüsselwörter

Matrix-Metalloproteinase 9 - tissue inhibitors of matrix metalloproteinases, TIMPs - TIMP-1 - akute Pankreatitis

Key words

matrix metalloproteinase 9 - TIMP-1 - tissue inhibitor of metalloproteinase 1 - acute pancreatitis

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