The role of cytokines in liver failure and regeneration: Potential new molecular therapies

Eithan Galun*, Jonathan H. Axelrod

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

108 Scopus citations

Abstract

The liver is a unique organ, and first in line, the hepatocytes encounter the potential to proliferate during cell mass loss. This phenomenon is tightly controlled and resembles in some way the embryonal co-inhabitant cell lineage of the liver, the embryonic hematopoietic system. Interestingly, both the liver and hematopoietic cell proliferation and growth are controlled by various growth factors and cytokines. IL-6 and its signaling cascade inside the cells through STAT3 are both significantly important for liver regeneration as well as for hematopoietic cell proliferation. The process of liver regeneration is very complex and is dependent on the etiology and extent of liver damage and the genetic background. In this review we will initially describe the clinical relevant condition, portraying a number of available animal models with an emphasis on the relevance of each one to the human condition of fulminant hepatic failure (FHF). The discussion will then be focused on the role of cytokines in liver failure and regeneration, and suggest potential new therapeutic modalities for FHF. The recent findings on the role of IL-6 in liver regeneration and the activity of the designer IL-6/sIL-6R fusion protein, hyper-IL-6, in particular, suggest that this molecule could significantly enhance liver regeneration in humans, and as such could be a useful treatment for FHF in patients.

Original languageAmerican English
Pages (from-to)345-358
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1592
Issue number3
DOIs
StatePublished - 11 Nov 2002
Externally publishedYes

Bibliographical note

Funding Information:
J.H.A. and E.G. are supported by grants from the Israel Science Foundation and The Horowitz Foundation. E.G. holds the Sam and Ellie Fishman Chair in Gene Therapy.

Keywords

  • Cytokine
  • Liver
  • Regeneration
  • Stem cells

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