Effects of a new extracorporeal system using CTR on mortality and inflammatory responses to bacterial toxin-induced multiple organ dysfunction syndrome in rabbits.
OBJECTIVE
In the pathogenesis of multiple organ dysfunction syndrome (MODS) caused by bacterial infection, a complex series of systemically secreted bacterial toxins and cytokines are intensely associated. Our previous study demonstrated that a new adsorbent, CTR, was capable of removing cytokines and toxic shock syndrome toxin-1 (TSST-1) in vitro. Moreover, extracorporeal treatment with CTR reduced the high mortality rate and inhibited inflammatory responses in endotoxin-induced shock in rats. However, it is unclear whether CTR treatment will be an effective therapy for MODS. Here, we demonstrated the efficacy of a new extracorporeal system using CTR on MODS induced by bacterial toxins in rabbits.


METHODS
Direct hemoperfusion (DHP) apheresis with or without CTR for 120 min was performed in rabbits that had been intravenously infused with endotoxin and TSST-1. The mean arterial pressure was recorded and the plasma toxin and cytokine concentrations were measured during the treatment period. Mortality was assessed up to 7 days after exposure to the toxins. In addition, tissues specimens were examined using microscopy.


RESULTS
The mortality rates at 7 days after the injection of the toxins were 90 and 10% for the control and CTR groups, respectively. The plasma concentrations of TSST-1, tumor necrosis factor and interleukin-1 beta in the CTR group were significantly lower than those in the control group. Histopathological examination revealed that tissue damage, such as necrosis and depletion of lymphocytes in the spleen and mesenteric lymph node, was reduced in the CTR group, compared with that in the control group, at 24 h after toxin infusion.


CONCLUSIONS
The new adsorbent CTR improved the mortality rate in a MODS rabbit model by adsorbing TSST-1 and cytokines. Further development of CTR may expand the scope of extracorporeal therapies for patients with MODS.
Life Science Research Laboratories, Life Science RD Center, Kaneka Corporation, Hyogo, Japan. masaji.kawatsu@kn.kanaeka.co.jp
Masaji
M
Kawatsu
Jutaro
J
Wada
Mitsuaki
M
Kitano
Eiji
E
Ogino
Hiroshi
H
Sakurai
Shigeo
S
Furuyoshi
Nobutaka
N
Tani
D000818:Animals; D001427:Bacterial Toxins / Q000097:blood* / Q000633:toxicity; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood* / Q000633:toxicity; D004768:Enterotoxins / Q000097:blood* / Q000633:toxicity; D005260:Female; D007249:Inflammation / Q000517:prevention & control; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D016060:Sorption Detoxification / Q000379:methods*; D018089:Superantigens / Q000097:blood* / Q000633:toxicity; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D013997:Time Factors
D001427:Bacterial Toxins; D016207:Cytokines; D004731:Endotoxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal