IL-10 attenuates hepatic I/R injury and promotes hepatocyte proliferation.
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.


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.
Dinant
Sander
S
Department of Surgery, Surgical Laboratory, Academic Medical Center, Amsterdam, The Netherlands. dinant@amc.uva.nl
Veteläinen
Reeta L
RL
Florquin
Sandrine
S
van Vliet
Arlène K
AK
van Gulik
Thomas M
TM
D000818:Animals; D001646:Bile / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008099:Liver / Q000098:blood supply*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000517:prevention & control*
D015850:Interleukin-6; D011994:Recombinant Proteins; D016753:Interleukin-10; D009195:Peroxidase