Adeno-associated viral vector-mediated interleukin-10 prolongs allograft survival in a rat kidney transplantation model.
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.
Chen
B
B
Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Kapturczak
M H
MH
Joseph
R
R
George
J F
JF
Campbell-Thompson
M
M
Wasserfall
C H
CH
Atkinson
M A
MA
Tisher
C C
CC
Flotte
T R
TR
Agarwal
A
A
Chen
S
S
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D006084:Graft Rejection / Q000503:physiopathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D049452:Green Fluorescent Proteins; D007273:Injections, Intramuscular; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics* / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous
D016207:Cytokines; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D003404:Creatinine