Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/reperfusion injury.
BACKGROUND
Oxygen-derived free radicals (FRs) are critical mediators of ischemia/reperfusion injury. Inflammatory cytokines have been shown to play important roles in tissue injury. To examine the relationship between FRs and interleukin-1 (IL-1) in hepatic ischemia/reperfusion injury, we used interleukin-1 receptor antagonist (IL-1ra) to block endogenous IL-1 production in a rat model of hepatic ischemia/reperfusion.


METHODS
Female SD rats were subjected to 30 min of hepatic ischemia followed by reperfusion. The animals were divided into two groups, control group and IL-1ra-treated group, according to the rinse solution. In both groups, FR production, histological changes, and interactions between leukocytes and endothelial cells were analyzed in the course of reperfusion.


RESULTS
In the control group, production of FRs increased significantly after 60 min of reperfusion. After 60 and 180 min of reperfusion, histological examination showed atrophy and degeneration of hepatocytes. Hepatic microcirculation demonstrated a marked increase in the number of leukocytes adherent to endothelial cells and of injured cells after reperfusion. In the IL-1ra-treated group, IL-1ra pretreatment markedly reduced FR production after 60 min of reperfusion, the number of leukocytes adherent to endothelial cells, and tissue injury.


CONCLUSIONS
These data clearly show an important role for IL-1 in the induction of FR production, leukocyte adhesion, and tissue injury after hepatic ischemia/reperfusion injury.
Shirasugi
N
N
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Wakabayashi
G
G
Shimazu
M
M
Oshima
A
A
Shito
M
M
Kawachi
S
S
Karahashi
T
T
Kumamoto
Y
Y
Yoshida
M
M
Kitajima
M
M
D000818:Animals; D002450:Cell Communication; D004727:Endothelium / Q000166:cytology; D005260:Female; D005471:Fluoroscopy; D007375:Interleukin-1 / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology; D014682:Vena Cava, Inferior / Q000502:physiology
D007375:Interleukin-1; D017382:Reactive Oxygen Species; D008165:Luminol