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Kidney Int. 2008 Jun;73(12):1364-73. doi: 10.1038/ki.2008.18. Epub 2008 Mar 19.

Systemic gene therapy with interleukin-13 attenuates renal ischemia-reperfusion injury.

Author information

1
Department of Clinical Pharmacology, Faculty of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. m.sandovici@med.umcg.nl

Abstract

Ischemia-reperfusion injury is a leading cause of acute renal failure and a major determinant in the outcome of kidney transplantation. Here we explored systemic gene therapy with a modified adenovirus expressing Interleukin (IL)-13, a cytokine with strong anti-inflammatory and cytoprotective properties. When ischemia was induced we found that the IL-13 receptor is expressed in both the normal and experimental kidneys. Prior to the induction of ischemia, rats received adenovirus-IL-13, control adenovirus or saline. IL-13 plasma levels increased more than 50-fold in adenovirus-IL-13 treated animals, confirming successful IL-13 gene delivery. Histological analysis showed decreased tubular epithelial cell damage with adenovirus-IL-13 therapy, accompanied by reduced kidney injury molecule-1 expression. Interstitial infiltration by neutrophils and macrophages was reduced by half as was interstitial fibrosis and expression of alpha-smooth muscle actin. IL-13 treatment significantly diminished the expression of E-selectin, IL-8, MIP-2, TNF-alpha and MCP-1 mRNA. These results suggest that the use of systemic IL-13 gene therapy may be useful in reducing renal tubulointerstitial damage and inflammation caused by ischemia-reperfusion.

PMID:
18354382
DOI:
10.1038/ki.2008.18
[Indexed for MEDLINE]
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