Adeno-associated viral vector-mediated interleukin-10 prolongs allograft survival in a rat kidney transplantation model
Chen, B. ; Kapturczak, M. H. ; Joseph, R. ; George, J. F. ; Campbell-Thompson, M. ; Wasserfall, Clive H. ; Atkinson, Mark A. ; Tisher, C. C. ; Flotte, Terence R. ; Argarwal, A. ... show 1 more
Citations
Authors
Kapturczak, M. H.
Joseph, R.
George, J. F.
Campbell-Thompson, M.
Wasserfall, Clive H.
Atkinson, Mark A.
Tisher, C. C.
Flotte, Terence R.
Argarwal, A.
Chen, S.
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Keywords
Blood Urea Nitrogen
Creatinine
Cytokines
Dependovirus
Female
*Genetic Vectors
Graft Rejection
Graft Survival
Green Fluorescent Proteins
Injections, Intramuscular
Interleukin-10
Kidney
Kidney Transplantation
Models, Animal
Rats
Rats, Inbred Strains
Rats, Inbred WF
Transplantation, Homologous
Allergy and Immunology
Genetics and Genomics
Pediatrics
Subject Area
Embargo Expiration Date
Link to Full Text
Abstract
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.
Source
Am J Transplant. 2007 May;7(5):1112-20. Link to article on publisher's site