Balance between pro and anti-inflammatory cytokines in patients with acute alcoholic hepatitis.
The ability of endogenous IL-10 to modulate inflammatory response and to limit hepatotoxicity has been shown in several models of liver injury.


OBJECTIVE
The objectives of this study were to evaluate the relationship between liver disease and the balance between pro and anti-inflammatory cytokines in acute alcoholic hepatitis.


METHODS
Twenty-five patients with pure steatosis, 17 with cirrhosis and mild acute alcoholic hepatitis (discriminant function value<32) and 41 patients with cirrhosis and severe acute alcoholic hepatitis (discriminant function value >=32) were studied. Plasma levels of interleukin 10 (IL-10) and soluble TNF receptors (TNFsRp75 and 55) were analyzed using ELISA assays. Hepatocyte proliferative activity was assessed with proliferating cell nuclear antigen labeling index (PCNA-LI) on formalin-fixed paraffin embedded liver biopsy specimens.


RESULTS
In patients with steatosis, cirrhosis with mild and severe acute alcoholic hepatitis, the plasma levels of IL-10 were higher (P<0.05) than in healthy controls. Between day 1 and day 8, the TNFsRp55/IL-10 ratio increased by 137 +/- 47 in the 10 patients with severe acute alcoholic hepatitis treated with prednisolone who died within 2 months and by 9.3 +/- 14 in the 19 patients still alive at 2 months (P=0.031). In patients with severe acute alcoholic hepatitis, PCNA-LI on liver biopsy was negatively correlated with the TNFsRp55/IL-10 ratio increase from day 1 to day 8 (r=- 0.42, P=0.11). PCNA-LI was positively correlated with TNFsRp75/TNFsRp 55 ratio increase from day 1 to day 15 (r=0.52; p<0.05).


CONCLUSIONS
Our data suggest the anti-inflammatory system is up-regulated in patients with alcoholic liver disease. Nevertheless, in patients with severe acute alcoholic hepatitis, IL-10 production seems insufficient to modulate TNF-alpha cytotoxicity mediated by TNFRp55.
Naveau
Sylvie
S
Service d'Hépato-Gastroentérologie, Hôpital Antoine Béclère, 92141 Clamart Cedex, France, Assistance Publique-Hôpitaux de Paris. sylvie.naveau@abc.ap-hop-paris.fr
Balian
Axel
A
Capron
Frédérique
F
Raynard
Bruno
B
Fallik
David
D
Agostini
Hélène
H
Grangeot-Keros
Liliane
L
Portier
Alain
A
Galanaud
Pierre
P
Chaput
Jean-Claude
JC
Emilie
Dominique
D
D000208:Acute Disease; D001706:Biopsy; D016022:Case-Control Studies; D005234:Fatty Liver / Q000097:blood / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008099:Liver / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D015854:Up-Regulation
D005938:Glucocorticoids; D018809:Proliferating Cell Nuclear Antigen; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D011239:Prednisolone