HEPATOPROTECTIVE ROLE OF INTERLEUKIN-10 IN GALACTOSAMINE LIPOPOLYSACCHARIDE MOUSE-LIVER INJURY/

Background & Aims: Interleukin (IL)-10 is a potent antiinflammatory cy tokine. Its role in modulating liver injury induced by galactosamine a nd lipopolysaccharide (Gal/LPS) was investigated. Methods: The. effect s of recombinant IL-10 (rIL-10), anti-IL-10 monoclonal antibodies, or gadolinium chloride (GdCl3) pretreatment were studied in mice challeng ed with Gal/LPS. Tumor necrosis factor (TNF) alpha and IL-10 serum con centrations were measured and liver injury was assessed by alanine ami notransferase (ALT) serum concentrations and by histology. Results: (1 ) IL-10 is pvoduced early and together with TNF-alpha after Gal/LPS ch allenge. (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) Administrat ion of vIL-10 30 minutes before Gal/LPS decreases TNF-alpha (-67%, P = 0.02), ALI (-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 pretrea tment protects against hepatotoxicity, decreases TNF-alpha, but increa ses IL-10 serum concentrations. Conclusions: These results indicate th at IL-10 protects the liver in the Gal/LPS mouse model. Increased IL-1 0 and decreased TNF-a secretion ave potentially involved in the hepato protection observed after GdCl3 pretreatment.