Prolongation of liver allograft survival after interleukin-10 gene transduction 24-48 fours 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 f or 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 1x10(10) p.f.u. of replication-deficient adenovirus vectors harboring human IL-10 cDNA (AdCMVh IL-10) via the ileocecal vein before or after rat orthotopic liver transpla ntation. 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 huma n 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 li ver 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 a nd interferon-gamma mere expressed without expression of IL-4 and IL-10, Conclusions. The prolongation of survival of IL-10 cDNA transferred Liver a llografts might be due to inhibition of the early phase of alloimmune-respo nse by over expression of IL-10, despite the expression of IL-2 and interfe ron-gamma.