title: Thioredoxin in human and experimental sepsis.
abstract: BACKGROUND
  Thioredoxin (TRX) is assumed to be beneficial in acute inflammatory diseases because of its potent antioxidant properties and an inhibitory effect on neutrophil evasion into sites of inflammation.
  
  
  OBJECTIVE
  To compare plasma levels of thioredoxin in septic patients and to investigate the role of thioredoxin in a polymicrobial septic mouse model.
  
  
  METHODS
  A combined single-center noninterventional clinical observation study and randomized controlled experimental investigation.
  
  
  METHODS
  Intensive care unit of a university hospital and laboratories of four university hospitals.
  
  
  RESULTS
  To evaluate the role of TRX in sepsis, we measured TRX in plasma of septic patients and compared its levels in survivors and patients who did not survive sepsis. In addition, we examined the effect of neutralization of endogenous TRX as well as of treatment with recombinant TRX in a mouse peritonitis model of cecal ligation and puncture (CLP). We found that the serum plasma levels of TRX were significantly higher in patients with sepsis compared with healthy individuals. Furthermore, nonsurvivors showed even higher TRX levels than survivors of sepsis. The CLP septic mouse model revealed that neutralization of endogenous TRX impaired survival of septic mice, whereas treatment with recombinant TRX after CLP strongly enhanced the survival of mice.
  
  
  CONCLUSIONS
  Our results therefore demonstrate a critical role for TRX in the septic inflammatory response and suggest TRX as a potential therapeutic target for septic shock.
authors.affiliation: Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofer
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosenhagen
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Christian
authors.initials: C
authors.lastname: Bopp
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Zimmermann
authors.forename: Meike
authors.initials: M
authors.lastname: Goebel
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.forename: Kartrin
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Raoul
authors.initials: R
authors.lastname: Breitkreutz
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D015331:Cohort Studies; D003422:Critical Care; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D010538:Peritonitis / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D015996:Survival Rate; D013879:Thioredoxins / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D013879:Thioredoxins