Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice.
OBJECTIVE
Tumor necrosis factor alpha (TNF-alpha) release plays a pivotal role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) administration in D-galactosamine (GalN)-sensitized mice. Interleukin (IL) 10 is an anti-inflammatory cytokine that inhibits TNF-alpha synthesis and release both in vitro and in vivo and prevents lethality from experimental endotoxemia. The present study was designed to ascertain whether in vivo treatment with IL-10 protects mice against LPS/GalN-induced liver injury.


METHODS
Mice were treated with an intraperitoneal dose of LPS/GalN with or without IL-10 pretreatment. Liver injury was assessed biochemically and histologically, and plasma TNF-alpha levels, liver myeloperoxidase activity, and adhesion molecule expression were determined.


RESULTS
Administration of LPS in GalN-sensitized mice caused lethal shock and massive hepatic necrosis in almost 100% of the mice. The effect was associated with a significant increase in plasma TNF-alpha concentrations, liver myeloperoxidase activity, and up-regulation of adhesion molecules on liver specimens and circulating neutrophils. Pretreatment with IL-10 reduced plasma TNF-alpha concentrations and LPS/GalN-induced liver injury and lethality. Moreover, IL-10 reduced the LPS/GalN-induced liver neutrophil margination and up-regulation of adhesion molecules both on liver specimens and circulating neutrophils.


CONCLUSIONS
The present results suggest that IL-10 therapy could be useful in the treatment of TNF-alpha-mediated liver diseases.
Santucci
L
L
Istituto di Gastroenterologia Endoscopia Digestiva, Università degli Studi di Perugia, Italy.
Fiorucci
S
S
Chiorean
M
M
Brunori
P M
PM
Di Matteo
F M
FM
Sidoni
A
A
Migliorati
G
G
Morelli
A
A
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D005688:Galactosamine / Q000276:immunology*; D007114:Immunization; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000506:poisoning; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005688:Galactosamine; D009195:Peroxidase