title: Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Anesthesiology, Division of Intensive Care, Oulu University Hospital, Kajaanintie 50, Oulu, Finland. fpeltola@mail.student.oulu.fi
authors.forename: Fiia P
authors.initials: FP
authors.lastname: Gäddnäs
authors.forename: Meeri M
authors.initials: MM
authors.lastname: Sutinen
authors.forename: Marjo
authors.initials: M
authors.lastname: Koskela
authors.forename: Taina
authors.initials: T
authors.lastname: Tervahartiala
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Tuula A
authors.initials: TA
authors.lastname: Salo
authors.forename: Jouko J
authors.initials: JJ
authors.lastname: Laurila
authors.forename: Vesa
authors.initials: V
authors.lastname: Koivukangas
authors.forename: Tero I
authors.initials: TI
authors.lastname: Ala-Kokko
authors.forename: Aarne
authors.initials: A
authors.lastname: Oikarinen
mesh_terms: D000368:Aged; D001768:Blister / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000503:physiopathology*; D012720:Severity of Illness Index; D012867:Skin / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: D053505:Matrix Metalloproteinases, Secreted