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 μg/kg of endotoxin on the serum concentration of TNFα 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 μg/kg in control rats, in cirrhotic rats significant hypotension occurred at doses of 25, 50, 100 and 1000 μg/kg. Following the administration of endotoxin (25 μg/kg) the serum levels of TNFα were 140 times higher in cirrhotic than in control rats (89 835±21 090 vs. 625±137 pg/ml; P<0.001). Serum TNFα 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 μg/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.