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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.
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Authors
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.
Chen, S.
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Document Type
Journal Article
Publication Date
2007-05-26
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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.

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Am J Transplant. 2007 May;7(5):1112-20. Link to article on publisher's site

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DOI
10.1111/j.1600-6143.2007.01772.x
PubMed ID
17456199
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