Prolongation of liver allograft survival after interleukin-10 gene transduction 24-48 hours before donation.
BACKGROUND
Interleukin- (IL) 10 may be a potent regulator for controlling of allograft rejection. A single administration of IL-10 is not effective for controlling graft rejection. Gene transfer is an attractive vehicle for prolonging the expression of short-lived proteins.


METHODS
Donor or recipient livers were transduced with 1 x 10(10) p.f.u. of replication-deficient adenovirus vectors harboring human IL-10 cDNA (AdCMVhIL-10) via the ileocecal vein before or after rat orthotopic liver transplantation.


RESULTS
DA allografts given AdCMVhIL-10 24-48 hr before donation survived for more than 56 days in Lewis recipients, although DA allografts given the adenovirus vector 7 days or 6 hr before, and 3 days after transplantation were rejected within 30 days in recipients. Serum levels of human IL-10 in gene-transferred rats were maximum from day 2 to 7. The serum level of human IL-10 then decreased gradually, and human IL-10 was not detected by ELISA 30 days after gene-transduction. In gene-transduced long-term surviving liver allografts, IL-10 was expressed, and the expression of IL-4 was also up-regulated on posttransplant day 3, despite the expression of Th1 cytokines (IL-2 and interferon-gamma), although in rejected liver allografts, IL-2 and interferon-gamma were expressed without expression of IL-4 and IL-10.


CONCLUSIONS
The prolongation of survival of IL-10 cDNA transferred liver allografts might be due to inhibition of the early phase of alloimmune-response by over expression of IL-10, despite the expression of IL-2 and interferon-gamma.
Department of Surgery II, Faculty of Medicine, Hiroshima University, Japan.
H
H
Tashiro
K
K
Shinozaki
H
H
Yahata
K
K
Hayamizu
T
T
Okimoto
H
H
Tanji
Y
Y
Fudaba
H
H
Yamamoto
X
X
Fan
H
H
Ito
T
T
Asahara
D000818:Animals; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006084:Graft Rejection / Q000097:blood; D006085:Graft Survival / Q000502:physiology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D007376:Interleukin-2 / Q000097:blood; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013997:Time Factors; D014161:Transduction, Genetic; D014184:Transplantation, Homologous / Q000276:immunology
D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma