Hepatoprotective role of interleukin 10 in galactosamine/lipopolysaccharide mouse liver injury.
OBJECTIVE
Interleukin (IL)-10 is a potent anti-inflammatory cytokine. Its role in modulating liver injury induced by galactosamine and lipopolysaccharide (Gal/LPS) was investigated.


METHODS
The effects of recombinant IL-10 (rIL-10), anti-IL-10 monoclonal antibodies, or gadolinium chloride (GdCl3) pretreatment were studied in mice challenged with Gal/LPS. Tumor necrosis factor (TNF) alpha and IL-10 serum concentrations were measured and liver injury was assessed by alanine aminotransferase (ALT) serum concentrations and by histology.


RESULTS
(1) IL-10 is produced early and together with TNF-alpha after Gal/LPS challenge. (2) Anti-IL-10 pretreatment increases TNF-alpha (+443%, P = 0.04), ALT (+160%, P = 0.04) serum levels, and the percentage of severe necrosis compared with control monoclonal antibodies. (3) Administration of rIL-10 30 minutes before Gal/LPS decreases TNF-alpha (-67%, P = 0.02), ALT (-94%, P = 0.01) serum concentrations, and the proportion of severe necrosis. The hepatoprotective effect is still observed when rIL-10 is injected 30 or 120 minutes after Gal/LPS. (4) GdCl3 pretreatment protects against hepatotoxicity, decreases TNF-alpha, but increases IL-10 serum concentrations.


CONCLUSIONS
These results indicate that IL-10 protects the liver in the Gal/LPS mouse model. Increased IL-10 and decreased TNF-alpha secretion are potentially involved in the hepatoprotection observed after GdCl3 pretreatment.
Louis
H
H
Laboratory of Experimental Immunology, Department of Gastroenterology and Hepatopancreatology, Universite Libre de Bruxelles, Brussels, Belgium.
Le Moine
O
O
Peny
M O
MO
Gulbis
B
B
Nisol
F
F
Goldman
M
M
Devière
J
J
D000818:Animals; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D005688:Galactosamine / Q000633:toxicity*; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005688:Galactosamine; D005682:Gadolinium; C038958:gadolinium chloride