title: Therapeutic potential of plasma gelsolin administration in a rat model of sepsis.
abstract: BACKGROUND
  Gelsolin is an actin-binding protein found in the cytoplasm and in extracellular fluids including blood plasma. Plasma gelsolin concentration decreases after a wide range of injuries. We hypothesized that the repletion of gelsolin would limit inflammation and tissue injury in a rat model of sepsis using cecal ligation and double puncture (2CLP).
  
  
  METHODS
  Human plasma gelsolin (pGSN, 10mg in 1ml saline) was administered once immediately following surgery, and control 2CLP (2CLP Alb) and sham animals were injected with 1ml saline containing equimolar albumin. Treatments were administered intraperitoneally (IP), intravenously (IV), or subcutaneously (SC).
  
  
  RESULTS
  Gelsolin levels in the 2CLP Alb group were lower than in sham animals. Administration of pGSN increased levels when administered IV and SC, but not IP. Morbidity scores were significantly less severe in the 2CLP pGSN group than in the 2CLP Alb group when pGSN was administered IV and SC, but not IP. Furthermore, enzymatic activity indicative of tissue damage (lactate dehydrogenase and alanine transaminase) was significantly lower in 2CLP pGSN group when treated SC compared to 2CLP Alb group.
  
  
  CONCLUSIONS
  These data provide further evidence that exogenous gelsolin can reduce morbidity from sepsis.
authors.affiliation: University of Pennsylvania, Department of Bioengineering, School of Engineering and Applied Science, 240 Skirkanich Hall, 210 S., 33rd Street, Philadelphia, PA 19104, USA.
authors.forename: Taylor S
authors.initials: TS
authors.lastname: Cohen
authors.forename: Robert
authors.initials: R
authors.lastname: Bucki
authors.forename: Fitzroy J
authors.initials: FJ
authors.lastname: Byfield
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ciccarelli
authors.forename: Brenna
authors.initials: B
authors.lastname: Rosenberg
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
authors.forename: Susan S
authors.initials: SS
authors.lastname: Margulies
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D018260:Gelsolin / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D007249:Inflammation; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D016207:Cytokines; D018260:Gelsolin; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase