Document Detail


Adeno-associated viral vector-mediated interleukin-10 prolongs allograft survival in a rat kidney transplantation model.
MedLine Citation:
PMID:  17456199     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interleukin-10 (IL-10) is a pleiotropic cytokine that plays a pivotal role in the regulation of immune responses. Hence, we evaluated the effects of a recombinant adeno-associated viral vector 1 (rAAV1) encoding rat IL-10 (rAAV1-IL-10) in a rat model of kidney allograft rejection. Dark Agouti rat kidneys were transplanted into Wistar-Furth (WF) rats 8 weeks following a single intramuscular administration of either rAAV1-IL-10 or rAAV1-green fluorescence protein (GFP). Isografts (WF-WF) served as an additional experimental control. Both allograft and isograft recipients received daily cyclosporine (10 mg/kg) for 14 days after transplantation. Serum IL-10 levels increased at 8, 12 and 16 weeks following vector administration in rAAV1-IL-10-treated animals, but not in rAAV1-GFP and isograft groups. rAAV1-IL-10 treatment resulted in lower BUN and creatinine levels (p<0.001), as well as increased allograft survival rates from 22% to 90%. Allograft histological abnormalities were significantly attenuated in the rAAV1-IL-10-treated rats compared with those of rAAV1-GFP controls. Serum levels of proinflammatory cytokines such as growth-related oncogene were also significantly higher in the rAAV1-GFP group than in the rAAV1-IL-10 group. These data suggest delivery of IL-10 using a rAAV1 vector improves renal function and prolongs graft survival in a rat model of kidney transplant rejection.
Authors:
B Chen; M H Kapturczak; R Joseph; J F George; M Campbell-Thompson; C H Wasserfall; M A Atkinson; C C Tisher; T R Flotte; A Agarwal; S Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons     Volume:  7     ISSN:  1600-6135     ISO Abbreviation:  Am. J. Transplant.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-25     Completed Date:  2007-08-07     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  100968638     Medline TA:  Am J Transplant     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  1112-20     Citation Subset:  IM    
Affiliation:
Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Urea Nitrogen
Creatinine / metabolism
Cytokines / blood
Dependovirus / genetics*
Female
Genetic Vectors*
Graft Rejection / physiopathology,  prevention & control
Graft Survival / drug effects*,  physiology
Green Fluorescent Proteins
Injections, Intramuscular
Interleukin-10 / blood,  genetics*,  pharmacology*
Kidney / drug effects,  pathology,  physiology
Kidney Transplantation / pathology,  physiology*
Models, Animal
Rats
Rats, Inbred Strains
Rats, Inbred WF
Transplantation, Homologous
Grant Support
ID/Acronym/Agency:
AI057362/AI/NIAID NIH HHS; DK-067472-01/DK/NIDDK NIH HHS; DK-071023-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 130068-27-8/Interleukin-10; 147336-22-9/Green Fluorescent Proteins; 60-27-5/Creatinine

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