title: A novel adsorbent of circulating bacterial toxins and cytokines: the effect of direct hemoperfusion with CTR column for the treatment of experimental endotoxemia.
abstract: OBJECTIVE
  The current study examined the ability of a new adsorbent, CTR, to remove enterotoxins, toxic shock syndrome toxin-1 (TSST-1), and cytokines from blood and/or serum in vitro and the effects of the extracorporeal treatment with CTR column on mortality rate and inflammatory responses to endotoxic shock in vivo.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  University and company experimental laboratory.
  
  
  METHODS
  CTR is composed of porous cellulose beads to which a hydrophobic organic compound with a hexadecyl alkyl chain has been covalently bound to the surface as a ligand. Human/bovine serum and human blood samples in vitro and Male Wistar rats were used.
  
  
  METHODS
  CTR's ability to adsorb bacterial toxins and cytokines related to sepsis in serum and/or blood was examined with an in vitro batch adsorption protocol. In vivo, male Wistar rats were anesthetized and assigned to one of three groups (n=14 per group): Escherichia coli endotoxin (15 mg/kg intravenously) alone (endotoxemic), apheresis with control column without CTR for 120 mins (control column), or extracorporeal treatment with CTR column for 120 mins (CTR treatment).
  
  
  RESULTS
  With use of the CTR adsorbent, the adsorption rates were 50% to 90% for enterotoxins, TSST-1, and cytokines such as TNF-alpha and interleukin (IL)-6 in the batch tests. In vivo, the mortality rates at 8 hrs after endotoxin injection were 92%, 92%, and 14% for the endotoxemic, control column, and CTR treatment groups, respectively. Hypotension and elevated plasma cytokine concentrations and the infiltration of neutrophils of the lungs were less conspicuous in the CTR treatment group than in the other two groups.
  
  
  CONCLUSIONS
  CTR, a novel adsorbent, effectively adsorbed small- to middle-sized proteins, such as cytokines, enterotoxins, and TSST-1 in vitro. Direct hemoperfusion apheresis with CTR column reduced mortality and had inhibitory effects on the inflammatory responses during endotoxemia in vivo. These findings suggest that extracorporeal blood purification with CTR column may be available to use for patients with sepsis and/or endotoxemia.
authors.affiliation: Department of Emergency and Critical Care Medicine, Graduate School of Medical Science, Kanazawa University, Japan. takutaniyan@yahoo.co.jp
authors.forename: Takumi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Hirai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Tsuda
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Inaba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakurai
authors.forename: Shigeo
authors.initials: S
authors.lastname: Furuyoshi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Tani
mesh_terms: D000327:Adsorption; D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins / Q000493:pharmacokinetics*; D002482:Cellulose / Q000031:analogs & derivatives / Q000627:therapeutic use; D016207:Cytokines / Q000493:pharmacokinetics*; D004768:Enterotoxins / Q000493:pharmacokinetics*; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000628:therapy; D012772:Shock, Septic / Q000628:therapy*; D018089:Superantigens; D016019:Survival Analysis
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D002482:Cellulose