title: The tryptophan kynurenine pathway, neopterin and IL-6 during vulvectomy and abdominal hysterectomy.
abstract: BACKGROUND
  Surgery has wide ranging immunomodulatory properties of which the mechanism is poorly understood. In order to investigate how different types of surgery influence inflammation, we designed a longitudinal observational study investigating two inflammatory profiles of two separate patient groups undergoing gynaecological operations of differing severity. In addition to measuring the well known inflammatory markers neopterin and IL-6, we also determined the kynurenine/tryptophan ratio. This study was a prospective, single center, two-armed observational study involving 28 female patients. Plasma levels of tryptophan, kynurenine, neopterin and IL-6 were determined from samples taken at: 24 hrs pre-operative, prior to induction, ten minutes before the operation was expected to end, and at 24 and 96 hours post operative in patients undergoing abdominal hysterectomy and vulvectomy.
  
  
  RESULTS
  There were 15 and 13 patients included in the vulvectomy and abdominal hysterectomy groups, respectively. In this study we show that anesthesia and surgery significantly increases the enzyme activity of indoleamine 2, 3 dioxygenase (IDO) as measured by the kynurenine/tryptophan ratio (P=0.003), while maintaining stable neopterin levels. However, abdominal hysterectomy causes a considerable IL-6 increase (P<0.001).
  
  
  CONCLUSIONS
  Surgery and associated anesthesia cause a significant tryptophan level decrease while significantly increasing IDO activity. Both types of surgery produce nearly identical neopterin time curve relationships, with no significant change occurring in either group. However, even though neopterin is unaffected by the severity of surgery, IL-6 responded to surgical invasiveness by revealing a significant increase during abdominal hysterectomy.
authors.affiliation: Department of Anesthesiology, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. j.w.hol@erasmusmc.nl.
authors.forename: Jaap Willem
authors.initials: JW
authors.lastname: Hol
authors.affiliation: Department of Anesthesiology, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. r.j.stolker@erasmusmc.nl.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Stolker
authors.affiliation: Department of Anesthesiology, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. m.klimek@erasmusmc.nl.
authors.forename: Markus
authors.initials: M
authors.lastname: Klimek
authors.affiliation: Department of Anesthesiology, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. d.l.stronks@erasmusmc.nl.
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Stronks
authors.affiliation: Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, the Netherlands. d.fekkers@erasmusmc.nl.
authors.forename: Durk
authors.initials: D
authors.lastname: Fekkes
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007737:Kynurenine / Q000097:blood*; D008875:Middle Aged; D019798:Neopterin / Q000097:blood*; D011446:Prospective Studies; D014364:Tryptophan / Q000097:blood*; D014844:Vulva / Q000601:surgery*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan