Volume 66 - 2003 - Fasc.1 - Georges Brohée Prize
Modulation of liver injury by interleukin-10
Inflammation is commonly observed in liver diseases and is fre- quently complicated by fibrosis and cirrhosis in end-stage disease. The only curative treatment for cirrhotic patients is liver trans- plantation. However, organ shortage as well as an increasing organ demand call for early treatment of liver disease and prevention of fibrosis. Experimental data have shown the critical role of pro-inf- lammatory cytokines like tumor necrosis factor-alpha (TNF-a) and interferon-gamma (IFN-g) in the development of liver injury. Here, we review our work on the role of endogenously produced interleukin-10 (IL-10), a potent anti-inflammatory cytokine, in several experimental models of acute and chronic liver injury. First, in acute macrophage-mediated hepatitis induced by galacto- samine/lipopolysaccharide administration, IL-10 neutralisation led to a more severe liver damage, whereas IL-10 injection, even delayed, was able to limit liver necrosis. A similar protective effect of IL-10 was observed in acute T cell-mediated hepatitis induced by concanavalin A (Con A) injection. The immunoregulatory role of IL-10 was then established after repeated exposition to Con A. In carbon tetrachloride liver injury, two other properties of IL-10 have been suggested : modulation of hepatocyte proliferation and modulation of liver fibrosis. Finally, the potential therapeutic applications in human liver disease as well as the potential side effects are discussed. (Acta gastroenterol. belg., 2003, 66, 7-14).