Mechanisms of interleukin-6 protection against ischemia-reperfusion injury in rat liver

Laura Tiberio, Guido A M Tiberio, Lidia Bardella, Edoardo Cervi, Katia Cerea, Michel Dreano, Gianni Garotta, Anna Fra, Nadia Montani, Andrea Ferrari-Bravo, Francesco Callea, Piergiovanni Grigolato, Stefano M. Giulini, Luisa Schiaffonati

Research output: Contribution to journalArticlepeer-review

Abstract

Numerous animal studies simulating liver injury have demonstrated that interleukin-6 (IL-6) exerts a protective effect. This study was designed to further analyze the molecular mechanisms underlying the protective role of IL-6 in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at high doses reduces cell damage which occurs in ischemic-reperfused liver, while at low doses displays only a limited protective capacity, (ii) anticipates and enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver also at a low, more pharmacologically acceptable dose, (iii) sustains the acute phase response which is dampened in ischemic-reperfused liver, (iv) strengthens the heat shock-stress response shown by ischemic-reperfused liver and (v) overcomes the dysfunctions of the unfolding protein response found in ischemic-reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays a crucial role in the potentiation of the different protective pathways activated in ischemic-reperfused liver. Our data confirm that IL-6 is a potential therapeutic in liver injury of different etiologies and reveal novel mechanisms by which IL-6 sustains liver function after ischemia/reperfusion injury.

Original languageEnglish
Pages (from-to)131-142
Number of pages12
JournalCytokine
Volume34
Issue number3-4
DOIs
Publication statusPublished - May 21 2006

Keywords

  • Acute phase response
  • Cell damage
  • Heat shock response
  • Transcription factors
  • Unfolded protein response

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

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