High-density lipoproteins reduce the effect of endotoxin on cytokine production and systemic hemodynamics in cirrhotic rats with ascites.
OBJECTIVE
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.
Ramírez
María José
MJ
Liver Unit, Hospital Clínic Universitari, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Villarroel 170, Barcelona 08036, Spain.
Ibáñez
Angel
A
Navasa
Miguel
M
Casals
Elena
E
Morales-Ruiz
Manuel
M
Jiménez
Wladimiro
W
Arroyo
Vicente
V
Rodés
Juan
J
D000818:Animals; D001201:Ascites / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D002251:Carbon Tetrachloride; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008075:Lipoproteins, HDL / Q000008:administration & dosage / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride