New therapeutic targets in liver diseases

Many patients with liver diseases often encounter difficulties with therapy and ultimately require liver transplant to survive. Since many acute and chronic liver diseases are driven by immune-mediated mechanisms, there is a necessity to find new therapies that can inhibit these immune-based triggers and block liver damage.

In a study appearing in advance of publication in the April 1 print edition of the Journal of Clinical Investigation, Christian Trautwein, Christian Klein, and colleagues from Hannover Medical School identify new therapeutic targets in liver diseases.

There has been growing evidence that IL-6 is protective against many pathophysiological conditions in the liver. IL-6 is a protein called a cytokine, which has cell protective functions. In cells, IL-6 acts by binding to a specific receptor in the cell membrane, which then triggers activation of gp130, a signal transducing protein. Gp130 leads to the activation of a signaling pathway inside cells from the membrane to the nucleus called the Jak/Stat pathway.

The researchers used rodent models of liver damage that causes hepatitis and liver damage involving immune T cells. Their aim was to characterize mechanisms involved in mediating IL-6-–dependent protection. They demonstrate that IL-6/gp130/Stat3–dependent expression of two proteins in liver cells – KC and SAA2 – is essential in mediating the protective effect of IL-6.

This establishes the role of key protective factors in liver injury mediated by hepatitis and immune mechanisms. KC and SAA2 are two proteins that may be of interest in developing therapies to treat immune-mediated liver disease in humans.