Z Gastroenterol 2007; 45 - A3_01
DOI: 10.1055/s-2007-967837

Adenoviral gene delivery of interleukin-10 reduces hepatic ischemia-reperfusion injury in rats

M Froh 1, P Walbrun 1, S Netter 1, R Wiest 1, E Gäbele 1, J Schölmerich 1, C Hellerbrand 1
  • 1Klinik und Poliklinik für Innere Medizin I der Universität Regensburg, Regensburg

Aims: Ischemia-reperfusion injury to the liver occurs in trauma, hemorrhagic shock, and after hepatic surgery, including tumor resection and transplantation. Reactive oxygen species, produced by activated macrophages (in particular Kupffer cells) and neutrophils, play a critical role in the injury caused by ischemia-reperfusion. The multifunctional cytokine Interleukin–10 (IL–10) is known for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages.

AIM: Here, we investigated the effect of adenoviral gene delivery of IL–10 in an acute model of hepatic oxidative stress.

Methods: Oxidative stress was established using a warm ischemia-reperfusion model, where nearly 70% of the liver was made hypoxic by clamping the hepatic artery and a branch of the portal vein for 1 hr followed by restoration of blood flow. Three days prior to the experiments, animals were infected i.v. with 3×109 plaque-forming units (PFU) of adenoviral vectors expressing (human) IL–10 (Ad5.IL–10) or the reporter gene for enhanced green fluorescent protein (Ad5.EGFP). IL–10 expression was analyzed using quantitative PCR analysis and ELISA.

Results: Ad5.IL–10 caused a significant increase of hepatic IL–10 mRNA expression and IL–10 serum levels as compared to Ad5.EGFP-treated control animals. Increase of serum transaminases (ALT, AST) observed after hepatic ischemia-reperfusion was significantly reduced compared to controls. Furthermore, histopathological hepatic changes as focal necrosis and hepatic leukocyte infiltration seen in control animals were almost comletely absent in Ad5.IL10 infected animals.

SUMMARY AND Conclusions: Increased hepatic IL–10 expression can effectively reduce hepatic oxidative stress caused by hepatic ischemia-reperfusion. Adenoviral gene delivery used here should be seen as a proof of concept and supports the hypothesis that use of less immunogenic gene delivery systems or direct application of recombinant IL–10 has powerful therypeutic potential.