IL-10 Attenuates Hepatic I/R Injury and Promotes Hepatocyte Proliferation

Dinant, Sander; Veteläinen, Reeta L.; Florquin, Sandrine; van Vliet, Arlène K.; van Gulik, Thomas M.

doi:10.1016/j.jss.2006.09.018

« Previous Next »Journal of Surgical Research
Volume 141, Issue 2 , Pages 176-182, August 2007

IL-10 Attenuates Hepatic I/R Injury and Promotes Hepatocyte Proliferation

Sander Dinant, M.D.
- Department of Surgery, Surgical Laboratory, Academic Medical Center, Amsterdam, The Netherlands
- To whom correspondence and reprint requests should be addressed at Surgical Laboratory, IWO-1-173, Academic Medical Center, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Reeta L. Veteläinen, M.D.
- Department of Surgery, Surgical Laboratory, Academic Medical Center, Amsterdam, The Netherlands
Sandrine Florquin, M.D., Ph.D.
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
Arlène K. van Vliet, Ph.D.
- Department of Surgery, Surgical Laboratory, Academic Medical Center, Amsterdam, The Netherlands
Thomas M. van Gulik, M.D., Ph.D.
- Department of Surgery, Surgical Laboratory, Academic Medical Center, Amsterdam, The Netherlands

Received 26 April 2006 published online 02 June 2007.

Background

One of the most important determinants of the outcome of hepatic ischemia and reperfusion (I/R) injury is the onset of the inflammatory response. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. It inhibits the production of interleukin-6 (IL-6), which however, also is involved in priming hepatocyte proliferation. The aim of this study was to examine the protective effects and the influence on the regenerative response of exogenous as well as endogenous IL-10 in a rat model of hepatic I/R injury.

Materials and methods

Seventy percent Liver I/R was induced in male Wistar rats for 60 min followed by 24 h reperfusion. One group underwent a midline laparotomy with recombinant rat (rr)IL-10 administration (SHAM + IL-10). The other groups underwent 60 min ischemia with administration of saline (I/R + saline), rrIL-10 [at two different time-points, i.e., I/R + IL-10pre(ischemia) and I/R + IL-10end(ischemia)] or anti-rat IL-10 antibody (I/R + antiIL-10).

Results

Parenchymal damage, as assessed by plasma alanine aminotransferase and aspartate aminotransferase, was significantly reduced by rrIL-10 and by endogenous IL-10 (P < 0.05). Also, rrIL-10 significantly reduced IL-6 production and the accumulation of neutrophils in liver and lung tissue, as measured by myeloperoxidase activity. Necrosis and apoptosis were significantly reduced and hepatocyte proliferation was stimulated by rrIL-10.

Conclusions

RrIL-10 and, to a lesser extent, endogenous IL-10, attenuate damage and inflammation, while rrIL-10 also promotes proliferation after hepatic I/R injury in rats. Therefore, rrIL-10 has potential use to prevent I/R injury and to promote liver regeneration after partial liver resection with temporary inflow occlusion.

Key Words: liver, ischemia, reperfusion, interleukin-10, proliferation, apoptosis