Recombinant adenovirus vector Ad-hIL-10 protects grafts from cold ischemia-reperfusion injury following orthotopic liver transplantation in rats.
BACKGROUND
Interleukin 10 (IL-10), a Th2 type cytokine, modulates inflammatory responses by inhibiting the production of proinflammatory cytokines. This study was designed to investigate the protective effects of adenovirus-mediated human IL-10 (Ad-hIL-10) gene transfer on protecting grafts from cold ischemia-reperfusion injury following orthotopic liver transplantation in rats.


METHODS
Adenoviruses encoding hIL-10 or beta-galactosidase (Ad-lacZ) were injected via the superior mesenteric vein into prospective donor animals. The donor liver was harvested 48 hours after transduction, and stored for 12 hours at 4 degree centigrade in lactated Ringer's solution prior to transplantation. The rats were divided into saline, Ad-lacZ, and Ad-hIL-10 groups. Liver function test, histopathological examination, reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blotting were performed at 24 hours after transplantation in the three groups.


RESULTS
Liver function (ALT and AST) was significantly improved, and the Suzuki score was significantly decreased in the Ad-hIL-10 group. The levels of hepatic TNF-alpha, MIP-2, ICAM-1 mRNA, and NF-kappaB protein in the Ad-hIL-10 group were significantly decreased. The expression of hIL-10 mRNA was detected by RT-PCR in Ad-hIL-10-treated grafts but not in controls treated with saline or Ad-lacZ.


CONCLUSIONS
Donor pretreatment with Ad-hIL-10 down-regulates the expression of proinflammatory cytokines TNF-alpha, MIP-2, and ICAM-1 mRNA. hIL-10 protects against hepatic cold ischemia-reperfusion injury, at least in part, by suppressing NF-kappaB activation and subsequent expression of proinflammatory mediators.
Si
Zhong-Zhou
ZZ
Department of Organ Transplantation, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Li
Jie-Qun
JQ
Qi
Hai-Zhi
HZ
He
Zhi-Jun
ZJ
Hu
Wei
W
Li
Yi-Ning
YN
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007511:Ischemia / Q000150:complications*; D016031:Liver Transplantation / Q000009:adverse effects*; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014184:Transplantation, Homologous
D016328:NF-kappa B; D016753:Interleukin-10