Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice

Abstract

Background and Aims: Tumor necrosis factor α (TNF-α) release plays a pivotal role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) administration in D-galactosamine (GaIN)-sensitized mice. Interleukin (IL) 10 is an anti-inflammatory cytokine that inhibits TNF- α synthesis and release both in vitro and in vivo and prevents lethality from experimental endotoxemia. The present study was designed to ascertain whether in vive treatment with IL-10 protects mice against LPS/GaIN-induced liver injury. Methods: Mice were treated with an intraperitoneal dose of LPS/GaIN with or without IL-10 pretreatment. Liver injury was assessed biochemically and histologically, and plasma TNF-α levels, liver myeloperoxidase activity, and adhesion molecule expression were determined. Results: Administration of LPS in GaIN-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-α concentrations, liver myeloperoxidase activity, and up-regulation of adhesion molecules on liver specimens and circulating neutrophils. Pretreatment with IL-10 reduced plasma TNF-α concentrations and LPS/GaIN-induced liver injury and lethality. Moreover, IL-10 reduced the LPS/GaIN-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-α-mediated liver diseases.