Tumor necrosis factor soluble receptor p55 and lipid peroxidation in patients with acute alcoholic hepatitis.
OBJECTIVE
In experimental models, liver injury induced by ethanol, cytotoxic activity of tumor necrosis factor (TNF) -alpha is principally mediated by TNF receptor p55 (TNFRp55). Among the various mechanisms underlying the toxic effects of TNF-alpha, overproduction of reactive oxygen species seems to play a key role in mediating TNF-alpha-induced cytotoxicity. The aim of this study was to evaluate, in patients with alcoholic liver disease, whether alcohol TNFRp55-mediated hepatotoxicity could account for lipid peroxidation expressed by significant increase in serum thiobarbituric reactive acid substances (TBARS) content, and could be amplified by decrease in blood total glutathione content and decrease in plasma antioxidant protective capacity.


METHODS
We studied 27 patients with histological alcoholic liver disease (five fibrosis, six acute alcoholic hepatitis (AAH) without cirrhosis, four cirrhosis without AAH, and 12 cirrhosis with AAH. TNFsRp55 and TNFsRp75 plasma levels were measured using ELISA assays. Plasma lipid peroxidation was evaluated by the content of TBARS. Total glutathione (tGSH) content in blood was determined by a kinetic assay. The sensitivity of erythrocytes to an oxidative stress and the plasma antioxidant protective capacity were simultaneously determined by a simple method.


RESULTS
In the 18 patients with mild or severe AAH, the plasma levels of TNFsRp55 were negatively correlated with tGSH and were positively correlated with TBARS, with total bilirubin and with discriminant function. tGSH was positively correlated with plasma selenium. The plasma levels of TNFsRp75 were positively correlated with TBARS and with total bilirubin. There was no significant correlation with the mean inhibitory 50% plasma volume or with the percentage of hemolyzed erythrocytes.


CONCLUSIONS
Our data support the notions that, in patients with AAH, TNFsRp55 probably mediates cytotoxicity of TNF-alpha, and that cytotoxic effect could be amplified by tGSH depletion in enhancing lipid peroxidation.
Naveau
S
S
Service d'Hépato-Gastroentérologie, Hĵpital Antoine Béclère, Clamart, France.
Abella
A
A
Raynard
B
B
Balian
A
A
Giraud
V
V
Montembault
S
S
Mathurin
P
P
Keros
L G
LG
Portier
A
A
Capron
F
F
Emilie
D
D
Galanaud
P
P
Chaput
J C
JC
D000208:Acute Disease; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001663:Bilirubin / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D006519:Hepatitis, Alcoholic / Q000378:metabolism*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012995:Solubility; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D015703:Antigens, CD; D008054:Lipid Peroxides; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D001663:Bilirubin