title: Norepinephrine infusion increases interleukin-6 in plasma and cerebrospinal fluid of brain-injured rats.
abstract: BACKGROUND
  Significantly increased plasma and CSF IL-6 levels reflect underlying tissue damage following clinical and experimental traumatic brain injury (TBI). Catecholamines, used under clinical conditions to maintain adequate cerebral perfusion pressure, induce a sustained IL-6 release. Thus an additional elevation in IL-6 could aggravate brain edema in the acute posttraumatic phase. We studied the changes in plasma and cerebrospinal fluid (CSF) IL-6 levels 4 and 24 hours after experimental TBI and assessed possible time-dependent effects of norepinephrine infusion on IL-6 and brain edema.
  
  
  METHODS
  Paired plasma and CSF IL-6 measured at 4 and 24 hours following TBI (n=10) were compared to levels in non-traumatized rats (n=5). In a placebo-controlled trial, 20 brain-injured male Sprague-Dawley rats were randomized to receive norepinephrine or NaCl for 90 minutes at 4 or 24 hours after TBI. Plasma IL-6 was measured before, during, and after the infusion period. One hour after stopping the infusion, CSF IL-6 and hemispheric swelling were determined.
  
  
  RESULTS
  During the first posttraumatic day, plasma and CSF IL-6 levels were significantly increased compared to non-traumatized rats, reaching the highest values at 24 hours (p<0.05). Norepinephrine infusion significantly increased plasma IL-6 at 7 and 27 hours after TBI; IL-6 was significantly elevated in CSF only at 7 hours (p<0.05). Brain edema was not aggravated.
  
  
  CONCLUSIONS
  The norepinephrine-induced increase in plasma and CSF IL-6 suggests that concomitant norepinephrine administration needs to be considered when interpreting systemic and local changes in IL-6 levels in TBI patients.
authors.affiliation: Charité-Department of Neurosurgery, Berlin, Germany. stoverfam@bluewin.ch
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Sakowitz
authors.forename: Britta
authors.initials: B
authors.lastname: Schöning
authors.forename: Stefan
authors.initials: S
authors.lastname: Rupprecht
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Kroppenstedt
authors.forename: Ulrich W
authors.initials: UW
authors.lastname: Thomale
authors.forename: Christian
authors.initials: C
authors.lastname: Woiciechowsky
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Unterberg
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000097:blood* / Q000134:cerebrospinal fluid*; D004487:Edema; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D012965:Sodium Chloride; D009638:Norepinephrine