A novel adsorbent of circulating bacterial toxins and cytokines: the effect of direct hemoperfusion with CTR column for the treatment of experimental endotoxemia.
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.
Taniguchi
Takumi
T
Department of Emergency and Critical Care Medicine, Graduate School of Medical Science, Kanazawa University, Japan. takutaniyan@yahoo.co.jp
Hirai
Fumiyasu
F
Takemoto
Yasuhiro
Y
Tsuda
Kazunobu
K
Yamamoto
Ken
K
Inaba
Hideo
H
Sakurai
Hiroshi
H
Furuyoshi
Shigeo
S
Tani
Nobutaka
N
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
D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D002482:Cellulose