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J Hepatol. 2006 Jul;45(1):20-7. Epub 2006 Mar 20.

Interleukin-6 is a key mediator of the hepatoprotective and pro-proliferative effects of ischaemic preconditioning in mice.

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  • 1Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia.

Abstract

BACKGROUND/AIMS:

The biological effects of ischaemic preconditioning include NF-kappaB activation, increased TNF synthesis, stimulation of cell cycle entry and hepatoprotection against ischaemia-reperfusion (IR) injury. Low dose TNF initiates the priming phase of liver regeneration via NF-kappaB and IL-6. To determine whether (1) IL-6 is released during preconditioning and confers protection against hepatic IR injury, and (2) IL-6 could mediate the biological effects of preconditioning.

METHODS:

Wildtype (wt) and TNF-/- C57BL6 mice were subjected to 90 min partial hepatic ischaemia and 2-44 h reperfusion with or without prior 10 min ischaemic preconditioning. To restitute liver injury, TNF-/- mice were administered murine TNF 5 microg/kg iv 1 min prior to IR. Murine recombinant IL-6 (500 ng/kg iv) was administered 30 min prior to IR, either to wt mice or to TNF-/--repleted mice; in the latter case, 1 min before preconditioning.

RESULTS:

In wt mice, IL-6 attenuated hepatic IR injury and stimulated cell cycle entry. IR injury in TNF-repleted TNF-/- mice was not ameliorated by preconditioning. However, prior IL-6 administration conferred hepatoprotection (IL-6/preconditioned: 349+/-169 U/L vs vehicle/preconditioned: 1250+/-608 U/L, P<0.01).

CONCLUSIONS:

IL-6 is one likely mediator of the hepatoprotective and pro-proliferative effects of ischaemic preconditioning.

PMID:
16600417
[PubMed - indexed for MEDLINE]
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