Background/Aims
The biological effects of ischaemic preconditioning include NF-κB 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-κB
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 μg/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.
Keywords
Abbreviations::
ALT (alanine aminotransferase), EMSA (electromobility (gel) shift assay), IL-6 (interleukin-6), IR (ischaemia-reperfusion), NF-κB (nuclear factor-kappa B), PCNA (proliferating cell nuclear antigen), STAT3 (signal transducer and activator of transcription 3), TNF (tumour necrosis factor), TNF−/− (tumour necrosis factor-α knockout mice)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 16, 2006
Accepted:
January 26,
2006
Received in revised form:
December 16,
2005
Received:
August 22,
2005
Identification
Copyright
© 2006 Published by Elsevier Inc.
