1999 Volume 10 Issue 2 Pages 91-97
Antithrombin III (AT-III) supplement in severe sepsis has been thought to modulate not only coagulopathic function but also to regulate cytokine production or endothelial function. The purpose of this study is to reveal the effects of AT-III on cytokine production. [Material and methods] Wistar rats received either 250U/kg (250 group) or 500U/kg (500 group) of AT-III from a central venous catheter, while, the control group received saline alone. Thirty minutes later, 5.0mg/kg endotoxin was continuously infused for 3hrs. Blood samples were collected at 0, 3 and 6 hrs after endotoxin infusion and serum levels of rat tumor necrosis factor α (TNF), interleukin 4 and cytokine-induced neutrophil chemoattractant (CINC) were measured by ELISA. AT-III activity, fibrinogen, AST, ALT, platelet and WBC counts were examined at 6 hrs. [Results and discussion] AT-III activity was 120% in the 250 group and 170% in the 500 group. Depletion of platelet count and fibrinogen was prevented in the 500 group (p<0.05), which showed a so-called “supranormal level” of AT-III. Increases of AST and ALT were suppressed in both groups (p<0.05) Although TNF levels in the 500 group at 0 hrs was approximately half of that in the 250 group, the difference was not significant. No significant difference was seen in interleukin 4 nor CINC at any time point in the three groups. In conclusion, the organ protective effects of AT-III is not expressed by regulation of cytokine production, but might be expressed through coagulation control or endothelial regulation in the present endotoxemic rat.
