INTERLEUKIN-10 REDUCES LETHALITY AND HEPATIC-INJURY INDUCED BY LIPOPOLYSACCHARIDE IN GALACTOSAMINE-SENSITIZED MICE

Background & Aims: Tumor necrosis factor alpha (TNF-alpha) release pla ys a pivotal role in the pathogenesis of liver injury induced by lipop olysaccharide (LPS) administration in D-galactosamine (GalN)-sensitize d mice, Interleukin (IL) 10 is an anti-inflammatory cytokine that inhi bits TNF-alpha synthesis and release both in vitro and in vivo and pre vents lethality from experimental endotoxemia. The present study was d esigned to ascertain whether in vivo treatment with IL-10 protects mic e against LPS/GalN-induced liver injury, Methods: Mice were treated wi th an intraperitoneal dose of LPS/GalN with or without IL-10 pretreatm ent. Liver injury was assessed biochemically and histologically, and p lasma TNF-alpha levels, liver myeloperoxidase activity, and adhesion m olecule 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 significa nt increase in plasma TNF-alpha concentrations, liver myeloperoxidase activity, and up-regulation of adhesion molecules on liver specimens a nd 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 margina tion and Lip-regulation of adhesion molecules both on liver specimens and circulating neutrophils. Conclusions, The present results suggest that IL-IO therapy could be useful in the treatment of TNF-alpha-media ted liver diseases.