Journal of hepatology · 2004
High-density lipoproteins reduce the effect of endotoxin on cytokine production and systemic hemodynamics in cirrhotic rats with ascites.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Ramírez María José, Ibáñez Angel, Navasa Miguel, Casals Elena, Morales-Ruiz Manuel, Jiménez Wladimiro, Arroyo Vicente, Rodés Juan
Аннотация
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 microg/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 microg/kg in control rats, in cirrhotic rats significant hypotension occurred at doses of 25, 50, 100 and 1000 microg/kg. Following the administration of endotoxin (25 microg/kg) the serum levels of TNFalpha were 140 times higher in cirrhotic than in control rats (89?835+/-21?090 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 microg/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.
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 microg/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 microg/kg in control rats, in cirrhotic rats significant hypotension occurred at doses of 25, 50, 100 and 1000 microg/kg. Following the administration of endotoxin (25 microg/kg) the serum levels of TNFalpha were 140 times higher in cirrhotic than in control rats (89?835+/-21?090 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 microg/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.