title: Systemic gene therapy with interleukin-13 attenuates renal ischemia-reperfusion injury.
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.
authors: Department of Clinical Pharmacology, Faculty of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. m.sandovici@med.umcg.nl
authors: M
authors: M
authors: Sandovici
authors: R H
authors: RH
authors: Henning
authors: H
authors: H
authors: van Goor
authors: W
authors: W
authors: Helfrich
authors: D
authors: D
authors: de Zeeuw
authors: L E
authors: LE
authors: Deelman
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D015316:Genetic Therapy; D018793:Interleukin-13 / Q000097:blood / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000032:analysis; D007684:Kidney Tubules / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D053660:Receptors, Interleukin-13 / Q000819:agonists; D051437:Renal Insufficiency / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D019040:E-Selectin; D018793:Interleukin-13; D016209:Interleukin-8; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D053660:Receptors, Interleukin-13; D014409:Tumor Necrosis Factor-alpha