Portal de Periódicos da CAPES

IL-6 Promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy

2008; Elsevier BV; Volume: 42; Issue: 3 Linguagem: Inglês

10.1016/j.cyto.2008.03.012

1096-0023

Guido Alberto Massimo Tiberio, Laura Tiberio, Anna Benetti, Edoardo Cervi, Nadia Montani, Michel Dréano, Gianni Garotta, Katia Cerea, Nathalie Steimberg, GianPietro Pandolfo, Andrea Ferrari-Bravo, Giovanna Mazzoleni, Stefano Maria Giulini, Luisa Schiaffonati,

Liver Disease and Transplantation

Major hepatic resection in cirrhotic patients is associated with impaired liver regeneration and failure, leading to high peri-operative mortality. In this work, the causes of defective regeneration in cirrhotic liver and the utility of IL-6 treatment were investigated in an experimental model combining cirrhosis and partial hepatectomy in the rat. Relative to normal controls, decompensated cirrhotic animals showed decreased survival, while compensated cirrhotic animals showed similar survival but reduced hepatic DNA synthesis and newly regenerated liver mass amount. Defective liver regeneration was associated with a decrease in STAT3 and NF-kB activation, consistent with an increased accumulation of their respective inhibitors PIAS3 and IkBα, and with a decreased induction of Bcl-xL. Treatment with recombinant IL-6 enhanced survival of decompensated cirrhotic animals, while it did not affect survival of compensated cirrhotic animals but sustained liver regeneration, by restoring STAT3 and NF-kB activation and Bcl-xL induction to the levels found in normal controls. The pro-growth effects exerted by IL-6 treatment in cirrhotic liver were attained also at low, pharmacologically acceptable doses. In conclusion, our results suggest that IL-6 treatment may be therapeutic in major resection of cirrhotic liver.