Adeno-associated viral vector-mediated interleukin-10 prolongs allograft survival in a rat kidney transplantation model
Gene Therapy Center; Department of Pediatrics
Medical Subject Headings
Animals; 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
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.
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Citation: Am J Transplant. 2007 May;7(5):1112-20. Link to article on publisher's site