Hyper-IL-6 gene therapy reverses fulminant hepatic failure

Naama Hecht, Orit Pappo, Daniel Shouval, Stefan Rose-John, Eithan Galun, Jonathan H. Axelrod*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Fulminant hepatic failure is a catastrophic condition caused by massive hepatocellular apoptosis and necrosis. Inhibition of hepatocyte apoptosis and the enhancement of the endogenous potential for liver regeneration could potentially form an effective basis for treatment of this condition. In response to injury in the liver, IL-6 mediates the acute-phase response and induces both cytoprotective and mitogenic functions. Hyper-IL-6 is a superagonistic designer cytokine consisting of human IL-6 linked by a flexible peptide chain to the secreted form of the IL-6 receptor. In a mouse model of acute liver failure induced by d-galactosamine administration, a single low dose of a hyper-IL-6-encoding adenoviral vector, in contrast to an adeno-IL-6 vector, maintained liver function, prevented the progression of liver necrosis, and induced liver regeneration, leading to dramatically enhanced survival. Thus, hyper-IL-6 gene therapy may be useful for the treatment of fulminant hepatic failure, which is often fatal even following treatment by transplantation.

Original languageAmerican English
Pages (from-to)683-687
Number of pages5
JournalMolecular Therapy
Volume3
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank T.-C. He and B. Vogelstein for generously providing the AdEasy system, W. Lindenmaier for pGEMIRESgfp, H. Giladi for the control vector Ad.gfp, and M. Sapir and J. Raub for technical assistance in the histopathological preparation and analysis. E.G. holds the Sam and Ellie Fishman Chair in Gene Therapy. This study was supported in part by grants to S.R.J. from the Deutsche Forschungsgemeinschaft, Bonn, Germany.

Keywords

  • D-galactosamine
  • Fulminant hepatic failure
  • Gene therapy
  • Gp130 hyperstimulation
  • Hyper-IL-6
  • IL-6/sIL-6R

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