High-density lipoproteins reduce the effect of endotoxin on cytokine production and systemic hemodynamics in cirrhotic rats with ascites

Background/Aims: Hypersensitivity to endotoxin is a recognized feature in cirrhosis. High-density lipoproteins (HDL) have a high capacity to inactivate endotoxin. The aim was to determine if HDL reduces the effect of endotoxin on cytokine production and systemic hemodynamics in experimental cirrhosis. Methods: The study was performed in control and rats with carbon-tetrachloride induced cirrhosis with ascites. Hemodynamic parameters were determined before and after several doses of endotoxin. The effects of 25 mug/kg of endotoxin on the serum concentration of TNFalpha and mean arterial pressure (MAP) were determined after treatment with HDL (80 mg/kg) or saline. Results: Whereas endotoxin decreased MAP only at doses of 100 and 1000 mug/kg in control rats, in cirrhotic rats significant hypotension occurred at doses of 25, 50, 100, and 1000 mug/kg. Following the administration of endotoxin (25 mug/kg) the serum levels of TNFalpha were 140 times higher in cirrhotic than in control rats (89 835 :L 21090 vs. 625 +/- 137 pg/ml; P < 0.001). Serum TNFalpha was 80% lower in cirrhotic rats pretreated with HDL (18 890 +/- 5012 pg/ml; P < 0.001) than in those pretreated with saline. The administration of endotoxin (25 mug/kg) was associated with a significant lower decrease of MAP in cirrhotic rats pretreated with HDL than in those receiving saline (11.9 +/- 3.5 vs. 24.7 +/- 4.3 %; P < 0.05). Conclusions: HDL attenuates the increased effect of endotoxin on cytokine production and systemic hemodynamic in cirrhosis. (C) 2003 European Association for the Study of Liver. Published by Elsevier B.V. All rights reserved.