Portal triad occlusion induces endotoxin tolerance: role of portal congestion.
BACKGROUND
Portal triad occlusion (PTO) causes portal congestion and damages the intestinal mucosa, which is associated with portal endotoxemia. However, administration of a sublethal dose of endotoxin results in resistance to its toxic activities. We tested the hypothesis that portal congestion due to PTO induces endotoxin tolerance.


METHODS
Rats were subjected to PTO for 15 min. In Group 1, male rats underwent laparotomy and, 48 h after the surgery, a lethal dose of Escherichia coli lipopolysaccharide was administered. In Group 2, rats were subjected to PTO for 15 min. Then a lethal dose of LPS was administered 48 h after surgery. Group 3 was treated the same as Group 2, except that PTO was performed with portosystemic shunt. Group 4 was also treated same as Group 2, except that rats received polymixin B and neomycin by gavage to eliminate intestinal luminal bacteria before PTO. Survival was examined after the administration of a lethal dose of LPS. Changes in plasma levels of cytokine are also measured after the administration of LPS. The portal endotoxin level in each group after PTO was measured.


RESULTS
On survival test, only rats in Group 2 and Group 4 showed significantly higher survival rates. The portal endotoxin level was significantly elevated only in Group 2. The elevation of plasma cytokine levels (IL-6, TNF-alpha) and NO production (NO(2)(-)/NO(3)(-)) in Groups 2 and 4 were inhibited compare to those in Groups 1 and 3.


CONCLUSIONS
PTO induced LPS tolerance possibly due to portal congestion and subsequent visceral congestion.
Unno
Naoki
N
Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. unno@hama-med.ac.jp
Uchiyama
Takashi
T
Yamamoto
Naoto
N
Inuzuka
Kazunori
K
Sagara
Daisuke
D
Konno
Hiroyuki
H
D000818:Animals; D003250:Constriction; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000517:prevention & control*; D004731:Endotoxins / Q000378:metabolism / Q000633:toxicity; D006488:Hemostasis, Surgical / Q000379:methods*; D015850:Interleukin-6 / Q000097:blood; D007511:Ischemia / Q000601:surgery*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011169:Portal Vein / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha