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Published on: October 12, 2012
Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis
Fiia P Gäddnäs1, Meeri M Sutinen, Marjo Koskela
1Department of Anesthesiology, Division of Intensive Care, Oulu University Hospital, Kajaanintie 50, Oulu, Finland. fpeltola@mail.student.oulu.fi
Introduction:
Matrix metalloproteinases (MMPs) have various roles in inflammatory states. They seem to be able to modulate endothelial barriers and regulate the activity of chemokines and cytokines. The timely development of the levels during severe sepsis and thereafter have not been investigated. In addition it was of interest to study alterations of MMP-levels in intact skin, as the skin is the largest barrier against external pathogens and MMPs have not been studied at organ level in human sepsis. The aim of this study was to investigate the timely development of serum and skin MMP-2, -8 and -9 levels in human severe sepsis and their association with disease severity and mortality.
Methods:
Forty-four patients with severe sepsis and fifteen healthy controls were included in this prospective longitudinal study. The amounts of MMP-2, -8 and -9 were analyzed from serum at days 1, 4, 6, 8, and 10, and from skin suction blister fluid at days 1 and 5 from the beginning of severe sepsis. Additionally, samples from the survivors were obtained after three and six months.
Results:
The levels of MMP-2 and -8 were up-regulated in severe sepsis in comparison to healthy controls in skin blister fluid and serum. Compared to the controls MMP-9 levels were lower in sepsis from the fourth day on in serum and both the first and fifth day in skin blister fluid. Active forms of MMP-2 and -9 were present only in severe sepsis. The non-survivors had higher pro- and active MMP-2 levels than the survivors in skin blister fluid samples. Furthermore, MMP-2 levels were more pronounced in blister fluid and serum samples in patients with more severe organ failures. In the survivors at 3 and 6 month follow-up the MMP levels had returned to normal.
Conclusions:
MMP-2 and -8 are elevated in serum and blister fluid in severe sepsis, implying that they may play a significant role in the pathogenesis of severe sepsis and organ dysfunctions. Active forms of MMP-2 and 9 were only present in patients with severe sepsis, and higher MMP-2 levels in skin blister and serum were associated with more severe organ dysfunctions.
Insights
Matrix metalloproteinases (MMPs) like MMP-2 and MMP-8 increase in severe sepsis, impacting organ dysfunction. Active MMP-2 and MMP-9 forms appear only in sepsis patients, with higher MMP-2 linked to worse outcomes.
Area of Science:
- Biochemistry
- Immunology
- Pathophysiology
Background:
- Matrix metalloproteinases (MMPs) play roles in inflammation, endothelial barrier modulation, and chemokine/cytokine regulation.
- The temporal dynamics of MMP levels during severe sepsis and their impact on skin barrier function remain understudied.
- Investigating MMPs at an organ level in human sepsis is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To investigate the temporal development of serum and skin MMP-2, MMP-8, and MMP-9 levels in severe sepsis.
- To associate MMP levels with disease severity and mortality in sepsis patients.
- To examine MMP levels in intact skin as a major barrier against pathogens.
Main Methods:
- A prospective longitudinal study included 44 severe sepsis patients and 15 healthy controls.
- Serum MMP-2, -8, and -9 levels were analyzed at multiple time points (days 1, 4, 6, 8, 10) and at 3- and 6-month follow-ups for survivors.
- Skin suction blister fluid was sampled at days 1 and 5 of severe sepsis.
Main Results:
- MMP-2 and MMP-8 levels were elevated in sepsis patients' serum and skin blister fluid compared to controls.
- MMP-9 levels were lower in sepsis patients from day 4 onwards in serum and from day 1 in skin blister fluid.
- Active MMP-2 and MMP-9 forms were detected exclusively in severe sepsis patients, with higher MMP-2 associated with increased organ failure and mortality.
Conclusions:
- Elevated MMP-2 and MMP-8 in serum and skin suggest a significant role in severe sepsis pathogenesis and organ dysfunction.
- The presence of active MMP-2 and MMP-9 forms is specific to severe sepsis.
- Higher MMP-2 levels in skin and serum correlate with more severe organ dysfunction, highlighting its prognostic value.
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